Cerebrolysin[1] | Stroke | Placebo

Cerebrolysin Review – Wise Young


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CEREBROLYSIN REVIEW Wise Young, Ph.D., M.D. W. M. Keck Center for Collaborative Neuroscience Rutgers University, Piscataway, New Jersey 08540-8087 Cerebrolysin is a peptide mixture isolated from pig brain. Cerebrolysin is a neurotrophic peptidergic mixture produced by standardized enzymatic breakdown of lipid-free porcine brain proteins. Approximately 25% if low molecular weight peptides (<10K DA) and 75% are free amino acids, based on free nitrogen content [1]. The mixture has relatively high concentrations of magnesium, potassium, phosphorus, and selenium [2], as well as other elements [3, 4]}. Babenkova, et al. [5] compared the antioxidative properties of cerebrolysin, finding that it is about 300x less than trolox (vitamin E). Shown to be beneficial in Alzheimer’s disease, the drug has been studied since the early 1970’s and many double-blind studies have reported sustained improvements in memory, concentration%, mood and fatigue in, and vertigo ([url= http://www.alzforum.org/drg/drc/detail.asp?id=39]Source[/url]). The drug has been approved for treatment of Alzheimer’s disease. A company named [url=http://www.ebewe.com/]Ebewe Pharmaceutical[/url] makes the drug. Two derivatives of cerebrolysin are being tested, one called EO21 and the other N-PEP-12 [6]. Over 176 articles have been published since 1973 on the subject of cerebrolysin treatment of various neurological disorders. I will review this literature below. Clinical Studies

First developed in Russia, cerebrolysin is a pig brain extract that was first used in patients with cerebral arteriosclerosis in 1973 [7] as a parentally administered organ hydrolysate [8]. It was also used to treat infantile cerebral palsy [9], geriatric patients [10], and other conditions [11-19]. In 1976, Wenzel [20] gave cerebrolysin to 33 patients with chronic encephalopathy, reporting that the treatment influence encephalographic (EEG) rhythm and other changes. From the perspective western medicine, these early studies were at best anecdotal. All these studies were performed in Russia and published in mostly Russian journals. Routes of administration. Several studies compared different routes of administration. In 1989, Rakhmatov & Mirakhmedov [21] treated patients who have psoriasis and neurological symptoms,

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investigating different routes of administration, finding that injection into the earlobe was the most effective and economical. Cerebrolysin widely used in large numbers of patients in Russia. For example, in 1992, Mukhamedzhanov, et al. [22] treated 548 patients with perinatal encephalopathy with cerebrolysin injections into the earlobe. In 1993, Naidin, et al. [23] of the Burdenko Institute of Neurosurgery compared intravenous and ear-lobe administration of cerebrolysin, finding no difference between the two routes. In 2000, Vilenskii, et al. [24] administered cerebrolysin through endolumbar application after hemispheric stroke and observed improvement in the patient 12 hours later. Stroke. Starting in the 1990’s, more serious clinical studies of cerebrolysin were carried out. For example, in 1990, Ischenko & Ostrovskaia [25] compared cerebrolysin and various other agents on blood viscosity in 128 patients with circulatory encephalopathy, finding that cerebrolysin marked increased blood viscosity and suggesting that the drug be cautiously used in patients with ischemic blood circulation disorders. In Austria, Kofler, et al. [26] studied contingent negative variation (CNV) in 41 geriatric patients with moderate “organic brain syndrome” and showed that 10 infusions of cerebrolysin plus multi-vitamin infusions increased CNV amplitudes, compared to the placebo that received multivitamin. In another study, Kofler, et al. carried out psychometric measures in 27 patients with organic brain syndrome and treated with a course of ten cerebrolysin treatments, compared to 14 clinically comparable patients. In 1991, Vereschchagin, et al. [27] treated 30 patients with multi-infarct dementia and compared them with 30 patients that received placebo. Cerebrolysin improved memory, abstract thinking, and reaction time of the patients, confirmed with EEG-mapping. In 1994, Gusev, et al. [28] treated 30 patients with acute ischemic strokes with daily intravenous doses of 10, 20, 30 ml for 10 days, reporting that the treatment accelerated recovery in those with moderate strokes, compared to control subjects. Pruszewicz, et al. [29] gave cerebrolysin to severe central hearing loss and observed improvement in 36%. In 1996, Iakno, et al. [30] treated 20 patients with vascular dementia and showed EEG effects and the most improvement in patients with the least cognitive deficit. In 2004, Gafurov and Alikulova [31] treated 2 groups of patients with ischemic brain hemispheric stroke and showed efficacy.

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Pediatric Treatments. A number of Russian studies focused on children. In 1998, Gromova, et al. [2] gave cerebrolysin to 36 3-8 year old children with minimal cerebral dysfunction. Gruzman, et al. [32] used intravenous cerebrolysin injections to treat resistant forms of night enuresis in children. In 2000, Sotnikova, et al. [33] found that cerebrolysin (1 ml per 10 kg) increased CD19+ cells and CD4+ lymphocytes with normalization of serum IgG and IgA levels and CD16+ cells (NK) at one month after treatment, in children (age 3-8 years) with minimal cerebral dysfunction; in addition, cerebrolysin activated T helper cells in vitro. Sukhareva, et al. [34] treated 120 children (age 4-15 years) with “neurosensory hypoacusis” with “pharmacopuncture” using cerebrolysin and several other drugs, finding that this treatment improved speech intelligibility, headache, and other problems in 85% of cases. Sotnikova [35] gave cerebrolysin (1 ml/10kg) intramuscularly for one month to children with attention deficit syndrome, reporting that this resulted in “a simultaneous normalization of neurological and immune disorders and a reduction in the illness rate.” In 2003, Krasnoperova, et al. [36] gave cerebrolysin (0.1 ml daily for 5 days) to 19 children with childhood autism and 8 with Asperger’s syndrome (aged 2-8) and found positive effects in all the patients with Asperger’s syndrome and 89% of the patients with autism. Guseva and Dubovsakia [37] treated 646 children (age 8 weeks to 18 years) with optic nerve disease by giving retrobulbar cerebrolysin once daily, in combination with microcirculatory drugs, in the irrigation system, or just microcirculatory drugs alone through the irrigation system. Cerebrolysin turned out to be highly effective. Extrapyramidal hyperkinesis. In 1997, Kontsevoi, et al. [38] did an open-label study of cerebrolysin treatment of 30 Parkinson patients who had prolonged extrapyramidal complications from neuroleptic therapy, finding that cerebrolysin marked reduced severity of extrapyramidal symptoms in 46.6% of the patients and partial response in 26.6%. In 1999, Panteleeva, et al. [39] gave cerebrolysin and magme B6 (a drug) to 51 patients with diagnoses of schizophrenia or depression, suffering from extrapyramidal and somato-vegetative effects of neuroleptic and anti-depressive drugs. Both drugs reduced the hyperkinetic and cardiovascular side effects of neuroleptic drugs. In 2004, Lukhanina, et al. [40] examined the effects of cerebrolysin on EEG activity of 19 patients with Parkinson’s disease and 18 healthy controls, They found twofold

global function. et al. The patients all demonstrated a significant improvement in mental function. double-blind. An open prospective study in Russia assessed 25 patients with childhood autism (ages 3-8) and received 2 therapeutic courses of cerebrolysin. Roshchina. and fine motor function [41]. and other measures. compared to 23 patients treated only with amiridin. et al. Ruther. attention during task performance. In 2000. [46] pointed out that clinical trials cerebrolysin is able to induce brain repair in chronic injury and that the effects are long-lasting in patients. In 1998. cognitive activity. showing a clear sustained beneficial effect of cerebrolysin over placebo. et al. 45] pointed out cerebrolysin as a potential therapy for Alzheimer’s disease. [43] treated 645 demented patients with 30 ml of cerebrolysin daily for an average of 17. In 2000. strengthening of postexcitatory inhibition in the auditory system after paired stimulation. [47] found that cerebrolysin (30 ml) enhanced the beneficial effects of amridin (80 mg daily for 10 weeks) in 20 patients with Alzheimer’s. Alvarez. et al. [53] did a 28-week. [42] did a double-blind placebo control study of cerebrolysin in 120 patients with moderate Alzheimer’s dementia and found modest beneficial effects. Rainer.Cerebrolysin Review – Wise Young - Page 4 improvements in CNV mean amplitudes. Ruther. associated with memory improvement. perception. In 1997. placebocontrolled study of 4-week cerebrolysin treatment in 149 patients . In 1999. reporting that the treatment improved clinical global impression in 80% of the patients and significantly more in younger and less afflicted patients. indicating a “powerful disease modifying activity” of cerebrolysin. et al. [49] carried out a double-blind placebo-controlled multicenter study of cerebrolysin in 53 men and women with Alzheimer’s disease and found that the treatment significantly improved cognitive deficits and global function in patients with mild to moderate dementia. et al.8 days. several reviewers [44. In 1994. et al. and activities of daily patients with Alzheimer’s disease. et al. Molloy and Standish [50] suggested that cerebrolysin be given to patients with Alzheimer’s disease. Windisch. Windisch [52] concluded that three placebo-controlled double-blind randomized studies have shown significant improvements of cognitive performance. [51] evaluated 101 patients 6 months after completion of a 4-week course of 30 ml cerebrolysin or placebo. Bae. In 2001. [48] found that a single oral dose of cerebrolysin induced progressive increase in EEG signals within an hour and peaked at 6 hours in elderly patients. Alzheimer’s Disease. Ruether.

et al. [55] replicated previous studies and showed that cerebrolysin improved cognitive performance and global function of patients with Alzheimer’s disease. Alvarez. et al. [6] randomized 54 males and females (>50 years old) who have memory loss since early adulthood. a brain-derived neuropeptide that is much less potent that cerebrolysin but can be administered orally. Panisset. Crook.Cerebrolysin Review – Wise Young - Page 5 with Alzheimer’s disease. In 1995. Acute Stroke. to treatment with N-PEP-12. Muresanu. et al. [61] treated patients with partial optic atrophy with retrobulbar . [57] correlated ApoE4 genotype in patient with mild-to-moderate Alzheimer’s disease and efficacy of cerebrolysin therapy and cholinergic (exelon) therapy. 5 days per week. The effects were maintained for 3 months after end of treatment. [58] did a neuropsychological evaluation of Alzheimer patients treated with two doses cerebrolysin (10. 4 weeks) or placebo and showed that the cerebrolysin treatment is well tolerated and significantly improved global score for 2 months after end of active treatment. as well as activities of daily living.2 point difference in the ADAS-cog scale. showing a 64. They found improved memory score and other clinical ratings. [56] randomized 192 patients with Alzheimer’s disease to cerebrolysin (30 ml. The results indicate a reversed Ushaped dose-response relationship. The higher dose was more effective and the patients showed better cognitive function and less disease progression. 30. Gavrilova. A 4-month treatment showed that cerebrolysin was 1. [59] did a 24week double-blind placebo-controlled study of 10. In 2006.7 fold higher than the exelon group but further analysis revealed that those with genotype ApoE4(-) had 3-fold higher effect from cerebrolysin than people with ApoE4(+).4% in the placebo group. The treatment was repeated at after a 2-month therapy-free period and improvements were maintained [54]. Domzai & Zaleska [60] treated 10 patients with acute middle cerebral artery strokes with 15 mg of cerebrolysin for 21 days and found similar recovery compared to a larger group of 108 patients given other drugs. the higher doses showed significantly better global outcome impressions. et al. Roshchina. In 2005. 30 ml) over 19 months. as well as a 3. et al.5% responder rate on the clinical global impression compared to 41. et al. In 2002. Sidorenko. The 10 ml dose improves cognitive performance but while the 30 and 60 ml dose did not further improve cognitive function. et al. and 60 ml of cerebrolysin (5 days a week for the first four weeks and then 2 infusions per week for 8 weeks).

In 2004. the Barthel Index. improved visual acuity. 63] compared 318 stroke patients that received standard hemodilution with 100 patients that received hemodilution with cerebrolysin. compared to only 25% of control untreated patients. comparing 10. disorientation. [66] randomized 146 patients to placebo or cerebrolysin within 24 hours after stroke and examined at various times up to 90 days later. Deigner. et al. et al. good safety and tolerability. In the same year. Gorbachevskaya. In 1998. Ladurner. In 2000.Cerebrolysin Review – Wise Young - Page 6 injections of cerebrolysin and apparently saw “favorable” effects in 50% of cases. Rett syndrome. 30. et al. or cognitive deficits after neurosurgery.7% of the treated patients. giving them 20 ml of cerebrolysininfusion daily over 10 days. Diabetic neuropathy. Bisenbach. [67] treated 20 patients with type II diabetes. et al. In 1997. patients on cerebrolysin showed significant better cognitive function on the Syndrome Short Test. and extended visual field. comparing with an age matched placebo control group. Funke. [71] gave . [65] randomized 36 patients (age 45-85 years) with ischemic stroke of the carotid territory to cerebrolysin (10 ml/day or 50 ml/day) or placebo on day 3 of the stroke and found EEG improvement in 72. In 2000. In 2001. [64] did a remarkable double-blind placebo-controlled study showing that cerebrolysin increased parietal EEG signal in 48 healthy subjects subjected to transient brain ischemia. Matula and Schoeggl [69] suggested that cerebrolysin may be useful for preventing neurological deficits such as confusion. Skvortsova. [70] suggested that cerebrolysin may act in neurodegenerative diseases by preventing neuronal apoptosis. Cerebrolysin treatment resulted in significant subjective improvement of painful diabetic neuropathy for at least 6 weeks. While the cerebrolysin group showed no significant improvement in clinical neurological scores. reporting that the treatment (along with others) arrested the glaucomatous process. reporting the cerebrolysin accelerates recovery. or Clinical Global Impression when compared to the placebo group. and 50 ml doses. et al. Koppi & Barolin [62. Lunusova [68] used cerebrolysin to treat patients with persistent glaucoma. et al. Neuroprotection. Glaucoma.

anti-aging [79]. . Trojanova. ischemic encephalopathy [80]. Animal Studies Early animal studies did not shed much light on the mechanism of cerebrolysin. et al. et al. [73] was used to treat patients with brain trauma and found significant improvement in patient’s clinical outcomes during the first year with no adverse events. compared to control mixtures of amino acids. as well as EEG. Traumatic Brain Injury. attention level. The trial suggested stabilization of cognitive loss and prevention of progression of vascular dementia. as well as early accumulation and increase in granular secretions in the pituitary gland of animals. motor function. and non-verbal social communication. organic mental disorders [77]. multiple sclerosis [78]. [81] applied the hydrolysate on cultures of chick peripheral and central neurons and found that high concentrations reduced nerve fiber growth but increased migration of non-neuronal cells. [83] reported that single injections of cerebrolysin given intraperitoneally to rats did not change their resistance to anoxia but repeated (5x) dosing increased resistance of young female rats (35 day old) to anoxia and that higher doses also increased resistance of adult rats to anoxia. Wong. Cerebrolysin has been proposed for a wide variety of neurodegenerative disorders [75. et al. At 6 months after treatment. et al. Lindner. In 1975. [72] gave cerebrolysin for 28 days (15 mg/day) annually for 2 years to 42 patients in a double-blind placebo-controlled study. et al. In 2005.Cerebrolysin Review – Wise Young - Page 7 cerebrolysin to 9 girls with Rett syndrome (age 2-7 years). 67% of the patients in the cerebrolysin group attained good outcome (GOS 3-5) compared to a historical cohort.005-0. [74] reported a beneficial effect of cerebrolysin on moderate and severe head injury patients.025 ml of the hydrolysate to neonatal rats and reported earlier differentiation of cytoarchitectonic fields in cerebral cortex. Zommer & Kvandt [82] gave doses of 0. 76]. and nucleotides. Alvarez. oligopeptides. Arteriosclerosis. Treatment resulted in increased behavioral activity. In 2001. In 1976. Vereshchagin.

They found cerebrolysin treatment or cerebrolysin with NGF eliminated retrograde amnesia in the rats. Japan examined the effects of cerebrolysin (FPF1070) on septal cholinergic neurons after transection of the fimbria-fornix in rat brain. 5. et al. lactic acid.Cerebrolysin Review – Wise Young - Page 8 Neural Development and Cerebral Metabolism. et al. They had found that intraperitoneal injections of the aqueous mixture of protein-free solution (containing 85% free amino acid and 15% small peptides) stimulated growth of embryonic dorsal root ganglion cultures. several Japanese groups started to study cerebrolysin. [94] showed . Wenzel. [84] reported that cerebrolysin treatment significantly increased the number of dendritic spines the dentate gyrus in neonatal rats. Immune Modulation. Cruz. In 1985. sulfocerebrosides and gangliosides in rats subjected to experimental demyelination and treated with cerebrolysin. 7 or 14 days and examined cerebral protein. Experimental Demyelination. Belokrylov and Malchanova [89] reported that treatment with cerebrolysin increased the number of Thy-1 positive cells and in vivo immune responses. [91] of Kinki University in Osaka. the FPF1070 mixture prevented degeneration and atrophy of injured cholinergic neurons. In 1991. and oxygen consumption of brain homogenates. Windisch & Poiswanger [85] treated rats for 3. By the 1980’s. et al. et al. Zuber [88] examined the effects of cerebrolysin on brain phospholipids in rats with experimental demyelination. In 1992. several groups reported the cerebrolysin affected neuronal development and cerebral metabolism in animals. In 1998. In 1998. 93] compared intraperitoneal cerebrolysin with different concentrations of intraventricular infusions with NGF and bFGF on amnesia induced by fimbria-fornix transections. In the early 1990’s. Akai. Apparently. In 1981. [87] assessed brain cerebrosides. Francis-Turner & Valouskova [92. Grechko [90] compared cerebrolysin with a number of other peptide immunomodulators drugs and found that cerebrolysin had greater effect on free open-field group behavior of animals than most. Fimbria-Fornix lesions. finding that higher doses (2.5 ml/kg) significantly increased respiratory activity of the homogenates. In 1996. In 1992. Bespalova. These effects apparently were most prominent in young rats up to 4 weeks and then in older 12-18 month old rats [86].

Ischemia. found that cerebrolysin potentiates GABA-A receptors in culture mouse hippocampal slices and that this could be blocked by bicucullin (a GABA-A receptor blocker). Baskys. and increases GLUT1 protein expression. proposed that cerebrolysin acted indirectly perhaps be release of endogenous adenosine.Cerebrolysin Review – Wise Young - Page 9 the cerebrolysin (2. et al. et al. Boado. Hippocampal slices. finding that it suppressed synaptic responses in CA1 neurons but not dentate gyrus neurons. Cerebrolysin also appears to inhibit hippocampal responses by activating the GABA-B receptor [107]. Xiong. [95] found that cerebrolysin preserved SOD and CAT activity in the brain after a septohippocampal lesion. et al. In 2000. suggesting that cerebrolysin modulates expression of BBB-GLUT-1 expression. [102] showed that both cerebrolysin and its peptide fraction EO21 increased the abundance of GLUT1 transporter in the brains of both old and young rats. Sugita. Boado [101] further showed that cerebrolysin stabilized GLUT1 transporter mRNA by increasing p88 TAF. In 1999. In 1995. Gonzalez. et al. Meanwhile. increases glucose uptake by the BBB. [109] assessed the effects of . Boado [98. 99] showed that cerebrolysin increased GLUT-1 expression via mRNA stabilization. Boado [103] showed that cerebrolysin markedly increases the expression of BBB-GLUT1 reporter genes containing regulatory cis-elements involved in stabilization and translation. In 1993. In 2000. et al. Zemkova. Boado [97] used a luciferin-luciferase reporter gene to show that cerebrolysin markedly increased the BBB-GLUT1 expression and that the mechanism did not involve phosphokinase C. [105. et al. Boado [96] at UCLA reported that cerebrolysin transiently increased the glucose transporter GLUT-1 in blood-brain-barrier (BBB) within 2 hours and then a reduction at 20-48 hours. Gschanes. [100] showed that acute or chronic administration of cerebrolysin increases the transport of glucose from blood to brain. In 2001.5 mg/kg x 7 days) had only a modest effect on glutathione related enzymes after fimbria-fornix transection. [108] of the Czech Republic. Blood-Brain Barrier. in 1995. In 1998. 106] found that cerebrolysin caused presynaptic inhibition that can be blocked with adenosine A1 receptor blockers and. In Toronto. et al. [104] assessed cerebrolysin effects on hippocampal slices. since cerebrolysin does not contain detectable amounts of adenosine. However.

Buresh. Cerebrolysin also improved EEG signal and motor activity of rats after mild forebrain ischemia [114]. Makarenko. They found the most pronounced effect for the cerebral-1 fraction and the 1. finding that cerebrolysin increased amplitude of evoked spreading depression. Veinbergs. et al. et al.2 subfraction. In 2000. Gannushkina. et al. et al. In 1999. Schwab. Koroleva. In 1999. et al. They measured the formation of hydroxyl free radicals in the brain and found that both DMSO (a hydroxyl free radical scavenger) and FPF1070 significantly reduced delayed neuronal death and evidence of hydroxyl radicals in the brains. Gschanes. [111] compared the effects of hypothermia and cerebrolysin. [118] studied the effects of cerebrolysin on 389 rats after bilateral common carotid occlusion. et al. et al. [120] found that cerebrolysin treatment protected the hippocampus against carbon monoxide poisoning and spreading depression. . Schwab. In 1998. et al. Schwab. [110] assessed the effects of cerebrolysin on cytoskeletal proteins after focal ischemia in rats. Bures. et al. In 1997. finding that the latter enhanced the neuroprotective effects of the former. [113] compared different fractions of cerebrolysin on a bilateral hemorrhagic rat stroke model. In 1997. [115] found that cerebrolysin improved spatial memory and motor activity in rats after ischemic-hypoxic injury. Cerebral excitability and hypoxia. et al.Cerebrolysin Review – Wise Young - Page 10 FPF1070 on delayed neuronal death in the gerbil global ischemia model. proposing that hydroxyl radical scavenging may be the mechanism of cerebrolysin effect. [116] showed that cerebrolysin (2. Koreleva. [112] showed that cerebrolysin reduced the size of cerebral infarct and microtubule protein loss after middle cerebral artery occlusion. et al. Masliah. [121] pre-treatment with cerebrolysin was necessary to provide significant neuroprotection for kainic acid injections. showing that the treatment did not increase blood flow but increased EEG recovery that may enhance ischemia damage. Alzheimer’s disease. In 1998. In the same year. [119] reported that cerebrolysin completely prevented hypoxia loss of CA1 neurons in the hippocampus. et al. In 2005.5 mg/kg daily x 10 days) remarkably protected the hippocampus against damage during repeated spreading depressions. [117] compared the effects of MK801 and cerebrolysin on focal ischemia. [122] showed that cerebrolysin ameliorates performance deficits and neuronal damage in apolipoprotein E-deficient mice (a model of Alzheimer’s disease).

The treatment significantly ameliorated performance deficits and protected neurons. Windolz. In 1998. In 1999. et al. Hutter-Paier. and IDE but did find higher levels of active cyclin-dependent kinase-1 (CDK5) and glycogen synthetase kinase-3 beta (GSK3beta). Cerebrolysin significantly reduced the amyloid burden in the frontal cortex of 5-month-old mice. Rockenstein. In 2003. Rockenstein. [126-129] reported that a single injection of cerebrolysin improved passive avoidance reactions in rats after transient cerebral ischemia. [138] reported that insulin-like . Rockenstein. et al. Valouskova and Gschanes [135] compared NGF. showing that cerebrolysin had a significant beneficial effect that declined to control levels by 8 months. In 1996. et al. et al. In 1999. Eder. [137] reported that cerebrolysin increased expression of the glutamate receptor subunit 1 (GluR1). In 1999. et al. In 1998. Reinprecht. [123] treated transgenic mice expressing human amyloid precursor protein (APP751) under the Thy-1 promoter. start 3 or 6 months after birth. as well as the levels of A-beta (1-42). et al. Spinal Motoneurons.Cerebrolysin Review – Wise Young - Page 11 In 2002. Nep. lasting up to 3 months after treatment stopped. Notch1. [134] gave cerebrolysin or EO21 to 24-month old rats and found that the peptide mixtures improved cognitive performance of the rats and increased number of synaptophysinimmunostaining in the hippocampus. [124] showed that cerebrolysin is neuroprotective in a transgenic mouse expressing human mutant amyloid precursor protein (APP) under the Thy1 promoter. et al. and cerebrolysin on rat performance in the Morris water maze test after bilateral frontoparietal cortical lesions. [136] found that cerebrolysin or EO21 increased synaptophysin immunoreactivity in the brains of 6-week old rats. Gschanes and Windisch [131] assessed the effects of cerebrolysin on spatial navigation in old (24-month) rats and found that cerebrolysin and EO21 (the concentrated peptide fraction of cerebrolysin) both improved spatial learning and memory of the rats. et al. Gschanes and Windisch [132] found that cerebrolysin or EO21 also improved spatial learning and memory in young rats. Memory. Haninec. [125] investigated various gene expression and found no change in BACE1. Gschanes & Windisch [130] likewise found that cerebrolysin improved spatial navigation in rats after transient brain ischemia. Valouskova and FrancisTurner [133] reported that cerebrolysin restored learning capability in rats when given 4 months after brain lesions. bFGF.

Mallory. et al.Cerebrolysin Review – Wise Young - Page 12 growth factor I (IGF-I) and cerebrolysin improves survival of motoneurons after ventral root avulsion. [1] showed that cerebrolysin is anti-apoptotic in embryonic chick cortical neuronal cultures and stimulates outgrowth and protection of neurites [150]. [151] showed cerebrolysin protects cultured chick cortical neurons from cell death from a wide variety of causes. Hypoglycemia. Hutter-Paier. iodoacetate. they propose that . Cerebrolysin also inhibits the calcium-dependent protease calpain [149]. [144] applied cerebrolysin to cultures of rat astrocytes and microglia. et al. et al. Cell Cultures. [139] showed that BDNF and cerebrolysin both increased reinnervation of the rat musculocutaneous nerve stump after avulsion and its direct reconnection with the C5 spinal cord segment. et al. In 2004. [142] showed that cerebrolysin counteracted the excitotoxic effects of glutamate and hypoxia [143] in cultured chick cortical neurons. et al. [140] studied the effects of cytoflavin or cerebrolysin in rats after spinal cord compression injury. [146] likewise showed that cerebrolysin reduced microglial activation both in vitro and in vivo. In 2005. Haninec. BDNF was better than cerebrolysin. Gutmann. including glutamate. Satou. In 1999. suggesting that it has synaptotrophic effects mediated through regulation of APP expression. In 2002. Alvarez. [147] reported that cerebrolysin had a inverted U-dose response on neurite growth and suggested that cerebrolysin has different effects depending on the subpopulation of neuron. [148] showed that cerebrolysin prevented MAP2 loss in primary neuronal cultures after brief hypoxia. [145] reported that cerebrolysin applied to the human teratocarcinoma cell line (NT2) markedly increased expression of synaptic-associated proteins. et al. Either IGF-1 or cerebrolysin were effective when given intrathecally to the spinal cord. et al. Patockova. Bul’on. Lombardi. Hartbauer. et al. and ionomycin. In 1998. showing that the peptide mixture prevented microglial activation after LPS activation and reduced interleukin-1b expression. The neuroprotective effects of cytoflavin were greater than for cerebrolysin. [141] showed that cerebrolysin significantly reduced lipid peroxidation induced by insulin hypoglycemia in the hearts and brains of mice. et al. et al. In 2001. Wronski. Spinal cord injury. et al.

It may also be useful for preventing progressive deterioration in Parkinson’s disease although no clinical trial has addressed this issue yet. There is some interest in using cerebrolysin to treat multiple sclerosis but both animal and clinical data are not yet available. et al. The treatment can even be delayed as long as 96 hours and still have beneficial effects. et al. There are efforts underway to develop an oral version of the drug. The data indicating beneficial effects of cerebrolysin on Alzheimer’s disease is very strong with nearly a dozen randomized clinical trials indicating efficacy and almost no study showing no or slight beneficial effects. The apparently broad spectrum of neuroprotective effects of the drug both in the acute and chronic phase of brain injury suggest that this drug should be useful for both acute and chronic stroke and traumatic brain injury. [153] found that a single addition of cerebrolysin to culture medium resulted in significant protection of tissue cultures against ischemia and hypoxia for up to 2 weeks.Cerebrolysin Review – Wise Young - Page 13 cerebrolysin stabilizes calcium ionic homeostasis. In 2006. Little data is available concerning the effect of the drug on spinal cord injury. Riley. Discussion and Summary Cerebrolysin is clearly an effective treatment for many neurological disorders. reducing apoptosis from 32% to 10%. . [154] applied cerebrolysin to organotypic brain slices and showed that the most pronounced neuroprotective effects of other drugs was seen when the drug was added both before and after glutamate. More studies are needed to ascertain the benefits of cerebrolysin for both acute and chronic spinal cord injury. ranging from stroke to Alzheimer’s disease. Schauer. Several studies suggest that the drug stabilizes excitability of the brain and can reduce hyperkinetic syndromes associated with neuroleptic drugs used for Parkinson’s disease. The side effects of the drug seem to be negligible. Safarova. The drug’s primary effect seems to be on the hippocampus but does seem to facilitate regeneration of spinal motoneurons and cerebral cortex. In 2005. Only one recent study is available regarding cerebrolysin therapy of a rat spinal cord compression model and it suggests a modest effect of the drug compared to another antioxidant. [152] showed that cerebrolysin improved survival of PC12 cells in serum-free medium. et al.

Int Clin Psychopharmacol.gov/entrez/query. [Use of cerebrolysin and ATP in treating infantile cerebral paralysis].nih. Mazina SS and Volkov A (2003).nih. Leng H. 98:27-30.gov/entrez/query.nlm.gov/entrez/query. Brozhik NS and Krotiuk LN (1973). 20:97-100. Avdeenko TV. [Effects of cerebrolysin on the oxidant homeostasis. Teselkin Iu O. 6. 108:459-73. Zh Nevrol Psikhiatr Im S S Korsakova. http://www. [Analysis of the content of ten kinds of metal elements in cerebrolysin by atomic absorption spectrophotometry]. 5.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9505400 Liu W.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=14681969 Babenkova IV. 115:22-4. Guang Pu Xue Yu Guang Pu Fen Xi. http://www. Makashova NV and Guseva MR (1999). 103:59-61.gov/entrez/query.nlm.nih. 4.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15729085 Zhovnir IK.ncbi. Effects of N-PEP-12 on memory among older adults. Laredo M and Moessler H (2005). Ferris SH.gov/entrez/query. 8. 21:397-9. Z Allgemeinmed. http://www. the content of microelements and electrolytes in children with minimal brain dysfunction].nih. Page 14 2.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=4786906 Gothe M (1974). a parenterally administered organ hydrolysate]. http://www.nlm.Cerebrolysin Review – Wise Young REFERENCES 1.gov/entrez/query.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10523962 Crook TH. Skal'nyi AV and Solov'ev OI (1998).ncbi. Kudrin AV. http://www.nih. Skofitsch G and Windisch M (2001). . [Antioxidative activity of histochrome and some other drugs used in ophthalmology]. Antiapoptotic effects of the peptidergic drug cerebrolysin on primary cultures of embryonic chick cortical neurons.nlm. http://www. [Therapy with Cerebrolysin. Zhu Z and Chen G (2001). 7. Vestn Oftalmol.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11475013 Gromova OA.nlm. http://www.ncbi. Zh Nevrol Psikhiatr Im S S Korsakova. Kataev SI. 50:588-9.ncbi. Pediatr Akus Ginekol.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=4839021 Gershman RN and Vasilenko MA (1975).ncbi. Hutter-Paier B.nih.gov/entrez/query. 11:109-11. [Use of cerebrolysin in patients with cerebral arteriosclerosis]. 9.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12947679 Gromova OA. Hartbauer M. 3.nih. Burtsev EM.gov/entrez/query. http://www. J Neural Transm. [Effects of cerebrolysin on trace element homeostasis in the brain].nlm.ncbi. Alvarez XA.nih. Vrach Delo.ncbi.

gov/entrez/query. [Findings in treatment with cerebrolysin]. Zh Nevropatol Psikhiatr Im S S Korsakova. Jassova Z and Medvecka E (1982). [Metalloligand homeostasis in hepatocerebral dystrophy]. Patol Fiziol Eksp Ter. 13.nih.ncbi.ncbi. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1226796 Jelasic F (1976). Med Welt. 31:636. http://www.nlm. 26:1937-9.ncbi.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=6858504 Osipenko TN. Z Allgemeinmed.ncbi.nlm.gov/entrez/query. 11616.ncbi. 12. http://www.nih. 23-7. 637.nlm. 17. [Clinical experience with Cerebrolysin in severe lesions of the cerebral cortex]. [Local .nih.gov/entrez/query.gov/entrez/query. Cesk Psychiatr.ncbi.nlm. http://www.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=7172295 Lekar PG and Botvinnik VS (1983).nlm.nih. [Clinical experience with Cerebrolysin in geriatrics]. 16.ncbi. [Therapeutic influence of cerebrolysin on the long-term stress barrier after an accident]. Med Welt.nlm. 52:1829-31. [Therapy with the cerebral hydrolysate cerebrolysin. http://www. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=6968055 Lekar PG. 28:1289-90. http://www.nih.nih. 11. 14.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1228606 Krauss W (1975). 83:9-13.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1186482 Wanderka H (1975). 86-8.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=7280806 Medvecky J.gov/entrez/query.gov/entrez/query. http://www.gov/entrez/query. Med Welt. 18.ncbi. Skvortsov IA and Korshunov SV (1991). [Treatment of hepatocerebral dystrophy (Wilson-Westphal-Konovalov's disease)]. http://www. Sov Med.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=895476 Bayer E (1980).Cerebrolysin Review – Wise Young - Page 15 10.nih.nlm. [Treatment of apoplectic attack using a higher single dose of Cerebrolysin]. ZFA (Stuttgart). 22-3. 15.nih. Makarova VA and Botvinnik VS (1981). A practice report]. 19.nlm. http://www.nih.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1014808 Sutterlin F (1977).nlm.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=7191468 Kosmarskaia EN and Butikova VI (1980).gov/entrez/query.ncbi. 78:308-11. [Effect of cerebrolysin on the function of the vestibulo-oculomotor and vestibulo-optokinetic systems in experimental postnatal hyperthyroidism].

gov/entrez/query.nih. 25.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8296505 Vilenskii BS.nlm.nlm.nih. 27. 21:145-9. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=2368364 Kofler B. An experimental psychological and electroencephalographic study (author's transl)].fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11247183 Ishchenko MM and Ostrovskaia OS (1990).nlm. http://www. [The principles of the combined rehabilitation of patients with perinatal encephalopathy and its sequelae]. 26.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1315467 Naidin VL and Krotkova OA (1993). Shirokov EA. MMW Munch Med Wochenschr. 28-30. Vestn Dermatol Venerol. http://www. Semenova GM and Grinevich TV (2000). 58-60.nlm. [The experience with endolumbar application of cerebrolysin in hemispheric ischemic stroke].nlm.ncbi. Nekrasova EM. http://www.nih.gov/entrez/query. 24. Solov'ev OI.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1661499 Wenzel E (1976).gov/entrez/query.ncbi. http://www.nih. 100:31-4. administration of cerebrolysin in Raynaud's disease in a 2-year-old child].ncbi. EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb.nlm. Vrach Delo.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=825764 Rakhmatov AB and Mirakhmedov UM (1989). http://www.gov/entrez/query. Zh Nevrol Psikhiatr Im S S Korsakova. Vozniuk IA.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=2633552 Mukhamedzhanov NZ. [Cerebrolysin electrophoresis in the correction of the mental defects in neurosurgery patients]. Odinak MM. Erhart P and Harrer G (1990).Cerebrolysin Review – Wise Young - Page 16 20.ncbi. [The treatment of psoriasis patients with concomitant neurological symptoms].ncbi. 118:1473-6.gov/entrez/query. 22.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=2123433 Vereshchagin NV.nlm.ncbi.gov/entrez/query. Piradov MA and Altunina MN (1991). [The effect of combined drug treatment on rheologic properties of the blood in patients with disordered circulatory encephalopathy]. 24-8.gov/entrez/query.nih. Zh Nevropatol Psikhiatr Im S S Korsakova. 43-5. Erhart C. Suslina ZA.ncbi. Lebedeva NV. [The effect of cerebrolysin on chronic encephalopathy. [The usefulness of event-related negativity in demonstrating the therapeutic effects of nootropic drugs using cerebrolysin as an example].nih.nih. http://www.nlm. Zh Vopr Neirokhir Im N N Burdenko. [Mild forms of multi- . 91:100-3. Kurbanova DU and Tashkhodzhaeva Sh I (1992). 21.gov/entrez/query.ncbi. http://www. Vopr Kurortol Fizioter Lech Fiz Kult. 23.

6-8.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=7970765 Iakhno NN. [The clinico-neurophysiological study of the effect of cerebrolysin on brain function in the acute and early recovery periods of hemispheric ischemic stroke].ncbi.nlm.gov/entrez/query. Levin OS and Elkin MN (1996).nih. 31.nlm. [Experience with using high doses of cerebrolysin in vascular dementia].gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12687163 Sukhareva MP. Otolaryngol Pol. http://www.gov/entrez/query.gov/entrez/query.ncbi. Novikova EA and Burtsev EM (2000).Cerebrolysin Review – Wise Young - Page 17 28.ncbi. [Pharmacopuncture in combined treatment of children with neurosensory hypoacusis]. 68:65-9.ncbi.ncbi. 24-6. Burd GS. 44-6. Gekht AB. Selikhova MV and Fidler SM (1994). 35.nih. Skvortsova VI.nih.nlm.nlm. Russ J Immunol.nlm. http://www. Gromova OA and Novicova EA (2002). Woznica B and Swidzinski P (1994). 48:63-6.gov/entrez/query. 94:9-13. Zh Nevrol Psikhiatr Im S S Korsakova.ncbi. Obrebowski A.nih.gov/entrez/query. 5:63-70. 30.nlm.gov/entrez/query. [Pharmacological possibilities in treatment hypoacusis in children]. Russ J Immunol. Immunoactive Properties of Cerebrolysin.gov/entrez/query. http://www. Ter Arkh.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1767322 Gusev EI. [Clinical and pathogenetical peculiarities and treatment policy in ischemic stroke of elderly and old age]. Zh Nevropatol Psikhiatr Im S S Korsakova. Sov Med.nih. 32. http://www.ncbi. 34.nlm. 7:357-64.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8009944 Pruszewicz A.nlm. 33. http://www.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9026950 Gafurov BG and Alikulova NA (2004).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11187070 Sotnikova NY.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15559220 Gruzman AV and Levina IN (1998). http://www.nih. Damulin IV. [The effect of cerebrolysin intravenous injections in resistant forms of night enuresis in children]. Vestn Otorinolaringol.ncbi. Zakharov VV.gov/entrez/query. http://www. Bogomolova MA.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12687248 . http://www. http://www. infarct dementia: effectiveness of cerebrolysin]. Gromova OA. 98:46. Aref'eva NA and Farkhutdinova LV (2000).nih. Zh Nevrol Psikhiatr Im S S Korsakova.nih. Dual effect of cerebrolysin in children with attention deficit syndrome with hyperactivity: neuroprotection and immunomodulation.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9845942 Sotnikova NY. 29.

fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=16075623 Kontsevoi VA. Krasnoperova MG.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11517474 Panteleeva GP. Goldsteiner H. [Effect of cerebrolysin on the electroencephalographic indices of brain activity in Parkinson's disease].nlm.gov/entrez/query. 39. Reiner C.Cerebrolysin Review – Wise Young 36. 147:426-31.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12872620 Guseva MR and Dubovsakia LA (2005). http://www. Karaban IN.gov/entrez/query.nih. http://www. Medvedev AV.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8159781 Rainer M. 27:32-40. 38. 42. Freytag S and Windisch M (1994). 99:3741.ncbi.nih.nlm. Ritter R. Vestn Oftalmol.ncbi. Zvenigorodskaia Iu V and Sheshenin VS (1997).nih.gov/entrez/query. Holl O.ncbi. [The efficiency of the use of cerebrolysin in optic nerve diseases in children of different age].nih. Zh Nevrol Psikhiatr Im S S Korsakova. [An effect of long-term cerebrolysin therapy in combination with neuroleptics on behavioral and cognitive disturbances in endogenous childhood autism]. Apecechea M. Page 18 37.gov/entrez/query. Zh Nevrol Psikhiatr Im S S Korsakova. Ender F. 43. Andrusenko MP.gov/entrez/query.nih.gov/entrez/query. Bondar VV. Efficacy of the peptidergic nootropic drug cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT). 40. Therapeutic results with Cerebrolysin in the treatment of dementia. 97:39-44.nlm.nlm. [Use of cerebrolysin in the treatment of prolonged extrapyramidal complications of neuroleptic therapy].nih. Zachhuber C and Mossler H (1997).ncbi.nlm. Skvortsov IA and Simashkova NV (2003). Krasnikova NI and Raiushkin VA (1999). Bashina VM.ncbi. 103:15-8. Burenok Iu A.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=16548370 Ruther E. http://www. Stossl J.ncbi. Mel'nik NA and Berezetskaia NM (2004).gov/entrez/query. 41. 121:17-20. [Cerebrolysin and magnesium-B6 in the treatment of side effects of psychotropic drugs]. Pharmacopsychiatry.nlm. http://www. Zh Nevrol Psikhiatr Im S S Korsakova. Wien Med Wochenschr.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15347036 (2006).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11530457 Lukhanina EP. 104:54-60. Kotlan P. http://www. Zh Nevrol Psikhiatr Im S S Korsakova. http://www. http://www. Brunnbauer M.nih.nlm. Dunky A. [The effect of cerebrolysin on cognitive functions in childhood autism and in Asperger syndrome]. Zh Nevrol Psikhiatr Im S S Korsakova. Paulitsch G. 106:21-5. .

J Neural Transm Suppl.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10961441 Ruther E. Ritter R.nih.nlm.ncbi. http://www.nlm.gov/entrez/query. Lee HS.Cerebrolysin Review – Wise Young - Page 19 44.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9408984 Grundman M.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15616667 Windisch M. 53:289-98. 59:293-300. http://www. Drug News Perspect.nih. Corey-Bloom J and Thal LJ (1998). 51. Sustained improvements in patients with dementia of Alzheimer's type (DAT) 6 months after termination of Cerebrolysin therapy.nlm. Cho H and Lee H (2000). 46.nih. 48:1566-71. Choi GD. Cho CY. Kim DH.ncbi. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10629930 Alvarez XA.gov/entrez/query. http://www. http://www. Laredo M.ncbi. Zharikov GA. Neurotrophic activities and therapeutic experience with a brain derived peptide preparation. Oral Cerebrolysin enhances brain alpha activity and improves cognitive performance in elderly control subjects.gov/entrez/query.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11129744 Molloy DW and Standish TI (2000).nih. Apecechea M. Corzo L.ncbi. Gmeinbauer R and Windisch M (2000). Zh Nevrol Psikhiatr Im S S Korsakova.ncbi. Freytag S. 49. 47.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700663 Nikolov R (1998). http://www.nih. Pichel V.ncbi. http://www.nlm. Hoon Oh B.gov/entrez/query.nlm. [The influence of cerebrolysin on the efficiency of subsequent therapy with amiridine++ in Alzheimer's disease patients (neuropsychological investigation)]. Clinical experience with Cerebrolysin. 50. Windisch M and Cacabelos R (2000).fcgi?cmd=Retrieve&db .nih. Gerasimov NP and Gavrilova SI (1999). J Am Geriatr Soc. Lombardi VR.nlm. 59:315-28. multicenter study of Cerebrolysin for Alzheimer's disease. Choi KG. Selezneva ND.gov/entrez/query. Hernandez A. Alzheimer's disease therapy . Jung SP.ncbi.gov/entrez/query. 99:43-6.nlm. Lorenzo R. J Neural Transm Suppl.nih. Lee S.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10961443 Bae CY. Cho K. J Neural Transm.gov/entrez/query. Sampedro C.gov/entrez/query. 11:248-55. 48. Freixeiro F.ncbi.nih.nlm. J Neural Transm Suppl.nih. http://www. Gschanes A and Hutter-Paier B (1998). 107:815-29.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700665 Roshchina IF.an update. placebo-controlled. Perez P.gov/entrez/query. A double-blind. 53:255-75. Alcaraz M. Kolykhalov IV. J Neural Transm Suppl. Perspectives in clinical Alzheimer's disease research and the development of antidementia drugs. 45. http://www.nlm.

J Neural Transm Suppl.gov/entrez/query. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10961442 Ruether E. Kalyn Ia B and Selezneva ND (2005). 277-85. Koper D. Ritter R. http://www. Approach towards an integrative drug treatment of Alzheimer's disease. Rainer M and Moessler H (2001).gov/entrez/query. Zh Nevrol Psikhiatr Im S S Korsakova. 265-75. http://www. Alvarez XA.nih. [Neuropsychological evaluation of longterm therapy of Alzheimer's disease using different cerebrolysin dosages].Cerebrolysin Review – Wise Young - Page 20 52.nlm. 55. 53. =PubMed&dopt=Citation&list_uids=11005546 Windisch M (2000). Gauthier S. 56. Sampedro C. Kolykhalov IV.ncbi.nih.nlm. J Neural Transm Suppl. Klingler D.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12456069 Muresanu DF.gov/entrez/query. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15704485 Alvarez XA. Husmann R. Rainer M and Moessler H (2002). 109:1089-104.gov/entrez/query. 58.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12111446 Gavrilova SI. Spatt J.nih. double-blind. double-blind.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15880838 Roshchina IF. placebocontrolled study with the neurotrophic agent Cerebrolysin. Int Clin Psychopharmacol.nlm.nih. Improved global function and activities of daily living in patients with AD: a placebocontrolled clinical study with the neurotrophic agent Cerebrolysin. J Neural Transm. Sustained improvement of cognition and global function in patients with moderately severe Alzheimer's disease: a double-blind. Zharikov GA. 105:27-34.ncbi. Moessler H and Windisch M (2002). Taneri Z. Cerebrolysin in Alzheimer's disease: a randomized.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11552768 Ruether E. Laredo M. Kasper S. Gavrilova SI. Cacabelos R. http://www. [ApoE genotype and efficacy of neurotrophic and cholinergic therapy in Alzheimer's disease]. Korovaitseva GI.nlm. 105:52-5. 16:253-63. 54. 59. 59:30113.gov/entrez/query. http://www.nlm. Kalyn Ia B.gov/entrez/query. Varela . Zharikov GA.nlm.ncbi. Couceiro V. Schmidt R.nih. Zh Nevrol Psikhiatr Im S S Korsakova.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12456070 Panisset M. http://www.nlm.gov/entrez/query.ncbi. Winterer W.nih.ncbi. A 28-week. 57.ncbi. placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease. Kinzler E. Rainer M and Moessler H (2002).nih. J Neural Transm Suppl. Kolykhalov IV and Selezneva ND (2005). placebo-controlled trial with a neurotrophic agent.ncbi. Diabl E.

http://www.nih.ncbi. Guseva MR.nih. Eichbauer-Sturm G and Zazgornik J .nlm.nlm. 112:415-28. 61. Fernandez-Novoa L.gov/entrez/query. 146:41-8.gov/entrez/query. doubleblind. [Hemodilution therapy with neuron metabolism specific therapy in ischemic stroke--encouraging results of a comparative study]. http://www. 53:385-98. A 24-week. [Cerebrolysin in the treatment of partial optic atrophy in children].ncbi. Aleixandre M.nih.gov/entrez/query. Tikhonova IV and Smychkov AS (2004).ncbi. Mewes I. Neurol Neurochir Pol. Zh Nevrol Psikhiatr Im S S Korsakova.nlm. doubleblind.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15559222 Ladurner G. Grafinger P. J Neural Transm.nlm.ncbi. Fiehler J.gov/entrez/query.nih. [Use of cerebrolysin in the treatment of ischemic stroke]. http://www. 64.Cerebrolysin Review – Wise Young - Page 21 60.nih. Shamalov NA. Neuroprotective treatment with cerebrolysin in patients with acute stroke: a randomised controlled trial. Wien Med Wochenschr. Stakhovskaia LV.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=7571926 Koppi S and Barolin GS (1996). Corzo L.ncbi. Muresanu D and Moessler H (2006). [A randomized.nlm.ncbi. 29:325-31.nlm. Granizo E.gov/entrez/query. 67. http://www. Rother I and Windisch M (1998).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15583955 Biesenbach G.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9819885 Funke M.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700674 Skvortsova VI. http://www. placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease. J Neural Transm Suppl. Dubovskaia LA and Lobanova IV (1995). Dose-dependent effects of Cerebrolysin on EEG and shortterm memory of healthy volunteers during control and hyperventilation induced cerebral ischemia.gov/entrez/query.nih. 66. 63.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8867272 Koppi S and Barolin GS (1998).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=16420392 Domzal T and Zaleska B (1995).gov/entrez/query. Zh Nevrol Psikhiatr Im S S Korsakova.nlm. 51-5. 98:30-3. Gubskii LV. Zh Nevropatol Psikhiatr Im S S Korsakova. M. Eur J Neurol. Kalvach P and Moessler H (2005).nlm. [Cerebrolysin in treatment of acute ischemic stroke]. 13:43-54. placebo-controlled study of Cerebrolysin safety and efficacy in the treatment of acute ischemic stroke]. 65. Vargas M.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=7566407 Sidorenko EI. Linares C. 95:51-4. http://www.nih. 62. http://www.ncbi.nih. http://www.gov/entrez/query. Eiselt M.

Cacabelos R.Cerebrolysin Review – Wise Young - Page 22 68.gov/entrez/query.ncbi. Zhu XL and Poon WS (2005).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11055224 Matula C and Schoeggl A (2000).nih. http://www. Vestn Oftalmol.nlm. Hernandez A. Laredo M.ncbi.nlm. (1997).nih. http://www. http://www. 95:59-60. during and after neurosurgical procedures. Int Clin Psychopharmacol. Arias D. [Efficiency in the dispensary care and surgical treatment of glaucoma patients].fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11740183 Deigner HP.ncbi. Maksimova M. 73. cognition and clinical outcome in patients with postacute traumatic brain injury: an exploratory study.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9173675 Iunusova GD (2000).ncbi. 23 Suppl 1:S90-3. [Cerebrolysin in treatment of painful diabetic neuropathy].nih. http://www. Haberkorn U and Kinscherf R (2000). http://www. Zas R.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11060707 Gorbachevskaya N.nlm. Corzo L. Varela M.nih. Figueroa J.gov/entrez/query. Expert Opin Investig Drugs.nlm.ncbi. Beneficial effect of cerebrolysin on moderate and severe head injury patients: result of a cohort study.nlm. Kashina EM. 74. 75:142-6. Positive effects of cerebrolysin on electroencephalogram slowing. Lombardi V.gov/entrez/query.gov/entrez/query. Perez P. [Treatment and prevention of cognitive dysfunction in patients with arterial hypertension and atherosclerosis: results of a randomized double-blind placebo-controlled trial of cerebrolysin]. Sampedro C.gov/entrez/query. Suslina ZA. 147:63-6.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=16463821 .ncbi. Pichel V.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11494441 Alvarez XA.ncbi. Aleixandre M and Moessler H (2003).ncbi. Apoptosis modulators in the therapy of neurodegenerative diseases. 116:35-7. Cerebral protection before. Stereotact Funct Neurosurg.nih. http://www.nlm. Cerebrolysin therapy in Rett syndrome: clinical and EEG mapping study. Bashina V. 71. Gnezditskii VV. http://www. Windisch M. Brain Dev.nih. Ter Arkh. 18:271-8.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12920387 Wong GK. 70. Wien Med Wochenschr. 69. 9:747-64.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11738849 Vereshchagin NV.nih.nlm. http://www. Timerbaeva SL.gov/entrez/query.gov/entrez/query.nih. Fernandez-Novoa L. 72.gov/entrez/query. Gratchev V and Iznak A (2001). Couceiro V. Acta Neurochir Suppl.nlm. Rebrova O and Smirnova IN (2001). 73:22-7.

82. 25:319-23. http://www.ncbi. 83. [Perspectives on the treatment of organic mental disorders by the use of nootropic agents].nlm.nih. [Effects of brain extract and hydrolysate on nerve tissue in vitro]. 105:42-5. [Apoptosis in neuronal structures and the role of neurotrophic growth factors.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12418396 Ukraintseva SV. 81.ncbi.nlm. Voen Med Zh. http://www.nih.nlm. http://www. http://www. [The effect of brain hydrolysate on central nervous system structure].gov/entrez/query.nlm.nih.fcgi?cmd=Retrieve&db . Z Mikrosk Anat Forsch.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1210977 Trojanova M.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12378888 Gomazkov OA (2002).nlm.nlm. http://www. 323:59-62.ncbi. Bisaga GN and Zarubina IV (2002). Grosse G. 102:69-70. [New approaches to antioxidant therapy in multiple sclerosis].ncbi. Zh Nevrol Psikhiatr Im S S Korsakova. Influence of cerebrolysin(r) on the resistance of rats to anoxia.nih. 17-21.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12747095 Litvintsev SV.ncbi.gov/entrez/query. Physiol Bohemoslov.gov/entrez/query.nih.gov/entrez/query.gov/entrez/query. 79. 75:1021-5. Zh Nevropatol Psikhiatr Im S S Korsakova. 89:815-23. http://www.ncbi. Gomazkov OA (2002).Cerebrolysin Review – Wise Young 75. [The effect of cerebrolysin on the clinical symptoms and the course of ischemic encephalopathy].nlm. Shamrei VK.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1086554 Zommer K and Kvandt I (1975). 77.gov/entrez/query. Biochemical mechanisms of brain derived peptide preparations].nlm. Pruzkova V and Mourek J (1976). Page 23 76. Ann N Y Acad Sci.nih.ncbi. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12073844 Odinak MM.nih. Zh Nevrol Psikhiatr Im S S Korsakova. Suppl:72-5.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15246996 Chukanova EI (2005). http://www. Antiaging treatments have been legally prescribed for approximately thirty years. Michalsky AI and Yashin AI (2004). Zh Nevrol Psikhiatr Im S S Korsakova. 1019:64-9. 80. http://www.ncbi. "Cerebrolysin: pharmacological effects and role in clinical practice"].gov/entrez/query.nlm. Matthies H and Kirsche W (1975). Karasek F. Arbeev KG.gov/entrez/query.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15704482 Lindner G. 78. Zh Nevrol Psikhiatr Im S S Korsakova. Reznik AM and Arbuzov AL (2002). [4th International Symposium.

nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=4084338 Windisch M and Piswanger A (1985).Cerebrolysin Review – Wise Young - Page 24 84.nlm. http://www.nih.nlm. ultrastructural and experimental study]. 85.ncbi.nih.ncbi. Nerv Sist. 89. Arzneimittelforschung.nlm. Eksp Klin Farmakol. Kliaich K. Arzneimittelforschung. http://www. 88. http://www. [Development of neuron structure of the fascia dentata in the rat. [The neurotropic activity of peptide immunomodulators]. 61:14-6. Sato T.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1817238 Zuber VL (1991). Ioku M and Hashimoto S (1992).ncbi. Neurohistologicomorphometric. http://www. 7:213-21. [Levamin and cerebrolysin as immunostimulants]. 91.ncbi.ncbi.nih. Chaeva LS and Mukhina AP (1991). 22:629-83. [The effect and changes in oxygen consumption of rat brain homogenates: in vitro effect of a peptide derivative].nlm. 30:64-71.gov/entrez/query.nih.ncbi. Nerve growth factor and nootropic drug Cerebrolysin but not fibroblast growth factor can reduce spatial memory impairment elicited by fimbria-fornix . Fujimoto M.gov/entrez/query. 92.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9783100 Akai F.nlm. [The effect of cerebrolysin on the metabolism of brain phospholipids in growing animals with experimental demyelination]. sulfocerebrosides and gangliosides in experimental demyelination and cerebrolysin administration]. 87. 30:85-90.gov/entrez/query. [The characteristics of the brain cerebrosides. 35:1353-6. Nerv Sist. http://www. J Hirnforsch.gov/entrez/query. Maksimova SP.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=7040546 Windisch M and Piswanger A (1985).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1611065 Grechko AT (1998).nih. 90.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1817241 Belokrylov GA and Malchanova IV (1992).ncbi. Histol Histopathol.gov/entrez/query. http://www. Hiruma S. http://www. Stender G and Duwe G (1981).nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=4074439 Bespalova MA.gov/entrez/query.nih. [Modification of rat brain metabolism by long-term treatment with a peptide derivative]. 86.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=1515704 Francis-Turner L and Valouskova V (1996). Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain.nlm. 113:165-6.nlm. Biull Eksp Biol Med. Iwamoto N. =PubMed&dopt=Citation&list_uids=135987 Wenzel J.gov/entrez/query. 35:1225-7. http://www.ncbi.

nlm.gov/entrez/query.ncbi. http://www. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8552293 97.ncbi. Wu D and Windisch M (1999).nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9832194 99.gov/entrez/query.gov/entrez/query. Boado RJ. Boado RJ (1998).Cerebrolysin Review – Wise Young - Page 25 transection: short-term study. http://www.ncbi. Rev Neurol. 47:277. Francis L and Castellano O (1998). Valouskova V and Mokry J (1996).gov/entrez/query.nih. Boado RJ (1998). http://www.ncbi. b-FGF and Cerebrolysin on the spatial memory after fimbria-fornix lesion in rats. Boado RJ (1995). Neurosci Res. Post-transcription modulation of the blood-brain . http://www. Boado RJ (2000).nlm. Francis L. 53:323-31.nih.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8841975 94.gov/entrez/query.gov/entrez/query.nlm. 34:217-24. Diaz-Suarez CM and Gonzalez-Fraguela ME (1998). Brain-derived peptides regulate the steady state levels and increase stability of the blood-brain barrier GLUT1 glucose transporter mRNA.nlm.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700669 96. The long-term effect of NGF.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9796003 95.nih. J Neural Transm Suppl.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8977147 98. 202:193-6.ncbi. Antioxidant systemic effect of short-term Cerebrolysin administration. Francis-Turner L. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10576544 101. 26:551-4. Neurosci Lett.ncbi.nlm.nlm. 53:333-41. http://www. Neurosci Lett. Neurosci Lett.gov/entrez/query. J Neural Transm Suppl. http://www. J Neural Transm Suppl. 197:179-82. Brain-derived peptides increase the expression of a blood-brain barrier GLUT1 glucose transporter reporter gene. Cruz R.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8848264 93. Gonzalez ME. 255:147-50. [Short-term effects of septo-hippocampal pathway transsection and cerebrolysin effects on glutathione-related enzymes in the rat brain].ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700668 100.nlm. Brain-derived peptides increase blood-brain barrier GLUT1 glucose transporter gene expression via mRNA stabilization. Molecular regulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived factors.gov/entrez/query.nih. Neurosci Lett. 220:53-6. http://www.ncbi.gov/entrez/query.nlm. In vivo upregulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides. Boado RJ (1996).nih.nih.ncbi.nih.

Kanazawa A. 45:325-31. Brain-derived peptides inhibit synaptic transmission via presynaptic GABAB receptors in CA1 area of rat hippocampal slices.ncbi.gov/entrez/query.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=7886083 Xiong H.nih. http://www. http://www.nih.ncbi. 32:71-7. http://www. 106.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11463479 Baskys A and Wojtowicz JM (1994). http://www.Cerebrolysin Review – Wise Young - Page 26 102.nlm. 108. Brain Res.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8930365 Zemkova H. Wojtowicz JM and Baskys A (1995).nlm.ncbi. Amplification of blood-brain barrier GLUT1 glucose transporter gene expression by brain-derived peptides.ncbi.nih.nih.fcgi?cmd=Retrieve&db .fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8841979 Xiong H. http://www. Physiol Res.nlm. Cerebrolysin.ncbi. Potentiation of GABAA receptor in cultured mouse hippocampal cells by brain-derived peptide mixture cerebrolysin.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10816070 Boado RJ (2001). 44:151-5. 105.nih.ncbi. Brain tissue hydrolysate acts on presynaptic adenosine receptors in the rat hippocampus.gov/entrez/query. Kondo T. Baskys A and Wojtowicz JM (1996). The drug cerebrolysin and its peptide fraction E021 increase the abundance of the blood-brain barrier GLUT1 glucose transporter in brains of young and old rats. acts on presynaptic adenosine receptors in the rat hippocampus.nlm.gov/entrez/query. Xiong H and Baskys A (1996). 104. 107.nih.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8564889 Wojtowicz JM.gov/entrez/query. http://www.nlm.ncbi.gov/entrez/query. 59:255-61.ncbi. J Neural Transm Suppl. 103. 49:1105-7. http://www. Pharmacol Biochem Behav.gov/entrez/query.nih.gov/entrez/query. 73:1194-7. Itou T and Mizuno Y (1993). Can J Physiol Pharmacol. 109. J Neural Transm Suppl.nih. [Protective effect of FPF 1070 (cerebrolysin) on delayed neuronal death in the gerbil--detection of hydroxyl radicals with salicylic acid]. Histochem J.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8869271 Sugita Y. Neurosci Res. Kruek J and Vyskocil F (1995). Boado R. barrier GLUT1 glucose transporter by brain-derived factors. Brain tissue hydrolysate.nlm.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10961437 Gschanes A. 737:188-94.nlm. Sametz W and Windisch M (2000). 40:337-42. No To Shinkei. http://www.nlm. http://www.gov/entrez/query. 47:281. Effects of brain tissue hydrolysate on synaptic transmission in the hippocampus.

nih.nlm. Koroleva VI. Nazimov IV. Valouskova V and Windisch M (1997).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8841977 Schwab M.nlm. 786:104-14. 112. Goloborod'ko EV and Pasikova NV (2005). 116.ncbi. Brain Res.nlm. http://www. Physiological effects and brain protection by hypothermia and cerebrolysin after moderate forebrain ischemia in rats.nlm.fcgi?cmd=Retrieve&db . Antonow-Schlorke I.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15934360 Schwab M. 68:15-20. 49:29-37. 104:1319-27.gov/entrez/query. 113.nih. Svinov MM.gov/entrez/query. Exp Toxicol Pathol. Loseva E and Bures J (1998). Durer U and Bauer R (1996). Zwiener U and Bauer R (1998). 114.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9085084 Schwab M. http://www.ncbi.ncbi. J Neural Transm Suppl. Korolev OS.nih.nih.gov/entrez/query.nlm. Exp Toxicol Pathol. Kositsin NS.ncbi.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9778808 Koroleva VI. [Shifts in the constant potential in the structures of the rat brain in focal ischemia and systemic hypoxia]. The effect of MK-801 and of brain-derived polypeptides on the development of ischemic lesion induced by photothrombotic occlusion of the distal middle cerebral artery in rats.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9085071 Gschanes A.nih. Effects of Cerebrolysin on cytoskeletal proteins after focal ischemia in rats. Ameliorative influence of a nootropic drug on motor activity of rats after bilateral carotid artery occlusion. http://www.nih.ncbi. =PubMed&dopt=Citation&list_uids=8334017 Schwab M.nih.gov/entrez/query. 111.Cerebrolysin Review – Wise Young - Page 27 110.nlm. Eksp Klin Farmakol.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9503278 Bures J.gov/entrez/query.ncbi.gov/entrez/query. Schaller R.nih.gov/entrez/query. http://www. 49:105-16. [A comparative study of antistroke activity of the new drug "cerebral" and its fractions in rats]. http://www.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700666 Makarenko AN. 117. http://www. 47:279. Zh Vyssh Nerv Deiat Im I P Pavlova. J Neural Transm.gov/entrez/query. Bauer R and Zwiener U (1997).ncbi. J Neural Transm Suppl. 48:640-53. Korolev OS and Mares V (1998). 53:299-311. Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats. http://www. http://www. Bauer R and Zwiener U (1997). Antonow-Schlorke I. Morphofunctional effects of moderate forebrain ischemia combined with short-term hypoxia in rats--protective effects of Cerebrolysin. 115.

Crews L. 29:56979.gov/entrez/query.nlm. 125.Cerebrolysin Review – Wise Young - Page 28 118. Antelava AL and Baranchikova MV (1998). Neurosci Behav Physiol. Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer's disease. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12456076 Rockenstein E. Alford M. Changes in the constant potential in brain structures in rats during focal ischemia and systemic hypoxia. J Neural Transm Suppl.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9633187 Buresh Y. 816:618-27.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10596794 Koroleva VI. Torrance M.nih. 59:273-80. 123. Moessler H and Masliah E (2002). Veinbergs I.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9972690 Rockenstein E. Crews L. http://www. Koroleva VI. Cerebrolysin decreases . Hippocampal damage induced by carbon monoxide poisoning and spreading depression is alleviated by chronic treatment with brain derived polypeptides.gov/entrez/query. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity.ncbi.nlm. http://www. Mallory M and Masliah E (2000). Mante M. J Neural Transm.nih. Mallory M and Samuel W (1999). Pastalkova E and Bures J (1999). Adame A. Pharmacol Biochem Behav.ncbi. 112:269-82. Patol Fiziol Eksp Ter.nlm.nlm. and neuronal damage in apolipoprotein E-deficient mice.gov/entrez/query.gov/entrez/query. J Neural Transm Suppl. Mallory M.gov/entrez/query. Mante M. =PubMed&dopt=Citation&list_uids=9554970 Gannushkina IV. http://www.ncbi.nih. [Effect of the nootropic agent cerebrolysin in cerebral ischemia in rats with varying behavioral reactions in the open field test].nlm. Paulino A. Korolev OS and Maresh V (1999).nih.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9878887 Veinbergs I. Armasolo F. Cerebrolysin ameliorates performance deficits.nih. 3-8.nih. 121. Larrea G. 327-36. Mante M. Moessler H and Masliah E (2006). Windisch M. 62:239-45. 120.gov/entrez/query. Brain Res. Mante M. 124.nlm. http://www. Adame A. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10961439 Masliah E. Moessler H and Masliah E (2005). 119. Korolev OS.ncbi. Amelioration of the cerebrovascular amyloidosis in a transgenic model of Alzheimer's disease with the neurotrophic compound cerebrolysin.nlm. Rose JB. 122.ncbi. Windisch M.gov/entrez/query. Mares V.nih. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15657642 Rockenstein E.ncbi.

Can Cerebrolysin influence chronic deterioration of spatial learning and memory? J Neural Transm Suppl. Fruhwirth M.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8901141 Gschanes A and Windisch M (1996).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8841976 Gschanes A and Windisch M (1998).gov/entrez/query.nlm. 53:343-9. J Neural Transm Suppl. The influence of Cerebrolysin and E021 on spatial navigation of 24-month-old rats.nlm. http://www. Effects of two protein-free peptide derivatives on passive avoidance behaviour of 24-month-old rats.nih. 130. 133. Cerebrolysin protects neurons from ischemia-induced loss of microtubule--associated protein 2.gov/entrez/query.gov/entrez/query. Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats. J Neural Transm Suppl.ncbi.fcgi?cmd=Retrieve&db . 100:161-6. http://www.ncbi.nlm.ncbi.ncbi. J Neural Transm Suppl.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8901142 Hutter-Paier B. 131.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10212063 Valouskova V and Francis-Turner L (1998). 47:278.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8841972 Hutter-Paier B. 129.nlm. Death of cultured telencephalon neurons induced by glutamate is reduced by the peptide derivative Cerebrolysin.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700667 Gschanes A and Windisch M (1999).ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=8841974 Hutter-Paier B.nih. http://www.nih.nlm. Dosedependent behavioural effects of two protein-free peptide derivatives on the passive avoidance reaction of rats. 46:237-41. Grygar E and Windisch M (1996).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=16511867 Hutter-Paier B. The influence of Cerebrolysin and E021 on spatial navigation of young rats.ncbi.gov/entrez/query. Eggenreich U and Windisch M (1996).nlm.Cerebrolysin Review – Wise Young - Page 29 126. http://www.nih.ncbi. http://www. Arzneimittelforschung.ncbi. http://www.nlm. Eggenreich U and Windisch M (1996).gov/entrez/query. 127. 132. http://www.gov/entrez/query.nlm. 128.gov/entrez/query.gov/entrez/query. amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer's disease.ncbi. 53:313-21. Arzneimittelforschung. 47:267-73. Behav Brain Res.nih.nih. Grygar E and Windisch M (1996).nih. J Neural Transm Suppl. http://www. 46:242-6.nlm. http://www. J Neurosci Res.nih. 47:276.

Neuroprotective effect of cytoflavin during compression injury of the spinal cord.nih. Histochem J.nih. Stejskal L and Dubovy P (2003). Neurobiol Learn Mem. Gschanes A.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12197668 Haninec P.nlm. http://www. Samal F. 185:233-8. Houstava L and Stejskal L (2004). Houst'ava L. http://www.nlm.nih.gov/entrez/query.ncbi. 136. 31:395-401.nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15351925 Bul'on VV. Reinnervation of the rat musculocutaneous nerve stump after its direct reconnection with the C5 spinal cord segment by the nerve graft following avulsion of the ventral spinal roots: a comparison of intrathecal administration of brain-derived neurotrophic factor and Cerebrolysin.nlm. 139. Reinprecht I.and long-term study. 33:605-12. Marhol P and Tumova E (2003). Gschanes A. Effects of NGF. Histochem J. Windisch M and Fachbach G (2000).gov/entrez/query. 71:13249.nih.nih. Windisch M and Fachbach G (1999). Selina EN.gov/entrez/query.gov/entrez/query. http://www. Rescue of rat spinal motoneurons from avulsion-induced cell death by intrathecal administration of IGF-I and Cerebrolysin.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10816071 Eder P. 32:79-84.nlm.gov/entrez/query. and cerebrolysin on water maze performance and on motor activity of rats: short. 139:3946. Krsiak M. 140. Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 24-month-old rats.gov/entrez/query. Alekseeva LE and Sapronov NS (2005). Exp Brain Res. =PubMed&dopt=Citation&list_uids=9700670 Reinprecht I. Kovalenko AL. 135. http://www.nih.gov/entrez/query. Schreiner E.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12801087 Haninec P. Skofitsch G and Windisch M (2001).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10462225 Valouskova V and Gschanes A (1999). Histochem J. b-FGF.nlm.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=16027862 Patockova J. Kuznetsova NN. http://www. Ann Anat. Cerebrolysin inhibits lipid peroxidation induced by insulin hypoglycemia in the . 159:425-32.ncbi. Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 6-week-old rats.nlm.ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10082636 Windholz E.Cerebrolysin Review – Wise Young - Page 30 134. 141. Increased density of glutamate receptor subunit 1 due to Cerebrolysin treatment: an immunohistochemical study on aged rats.ncbi. Bull Exp Biol Med. 137.nih.ncbi. 138.ncbi. http://www. Dubovy P. http://www.

nlm.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700672 Hutter-Paier B. Cacabelos R and Windisch M (2000). 53:351-61. Physiol Res. Crailsheim K and Windisch M (2000). Hutter-Paier B. 59:263-72. Garcia M. http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11145001 Wronski R. brain and heart of mice.nlm.gov/entrez/query.ncbi. Kronawetter S. http://www.Cerebrolysin Review – Wise Young - Page 31 142.nlm. Cerebrolysin protects isolated cortical neurons from neurodegeneration after brief histotoxic hypoxia.nih. Ohde H.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10961440 Satou T. 59:281-92. 52:455-60. Further evidence that Cerebrolysin protects cortical neurons from neurodegeneration in vitro.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10961438 Wronski R.nlm. and sympathetic trunks.gov/entrez/query. 147.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=9700671 Lombardi VR.gov/entrez/query. 145.ncbi. Itoh T. Cagiao A. Neurotrophic effects of FPF-1070 (Cerebrolysin) on cultured neurons from chicken embryo dorsal root ganglia. Friedrich P and Windisch M (2000).fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12899658 Hutter-Paier B. Tompa P. http://www.nih.nlm. http://www.gov/entrez/query. J Neural . J Neural Transm Suppl.nih. J Neural Transm Suppl. Lombardi VR. Tamai Y.ncbi. Johnson R. Windisch M. Effects of Cerebrolysin on in vitro primary microglial and astrocyte rat cell cultures. Inhibitory effect of a brain derived peptide preparation on the Ca++-dependent protease. ciliary ganglia.nih. Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection. J Neural Transm Suppl. http://www. Steiner E and Windisch M (1998).nlm. Hsu L. Crailsheim K.nih.nih. J Neural Transm. Fernandez-Novoa L.ncbi. Honer W.nlm. calpain.gov/entrez/query. 148. Methods Find Exp Clin Pharmacol. http://www.ncbi.nih. In vitro synaptotrophic effects of Cerebrolysin in NT2N cells.gov/entrez/query. 21:331-8.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10334480 Alvarez XA. 53:36372. A brain derived peptide preparation reduces the translation dependent loss of a cytoskeletal protein in primary cultured chicken neurons. Garcia M and Cacabelos R (1999). http://www. Rockenstein E and Masliah E (1999).nih. http://www. 149.ncbi. Sampedro C. Fruhwirth M. Anderson AJ and Hashimoto S (2000).ncbi.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10420388 Mallory M.gov/entrez/query. 144.nlm. 97:437-46. J Neural Transm Suppl.gov/entrez/query. 146. 107:1253-62.ncbi. Grygar E. Temmel I and Windisch M (1998). Acta Neuropathol (Berl). 143. Hutter-Paier B.

Moessler H and Wronski R (2006).ncbi. HutterPaier B and Windisch M (2005). Doppler E. Transm.nlm.nlm. Moessler H.ncbi. J Neural Transm. 154. Trophic effects of nootropic peptide preparations cerebrolysin and semax on cultured rat pheochromocytoma.gov/entrez/query.nlm. Grivennikov IA and Myasoedov NF (2002). http://www.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12826494 Safarova ER. http://www.Cerebrolysin Review – Wise Young - Page 32 150.gov/entrez/query.gov/entrez/query. Effects of Cerebrolysin on the outgrowth and protection of processes of cultured brain neurons. Windisch M and Gmeinbauer R (2002).ncbi.ncbi. J Neural Transm. http://www. 152. Neuroprotection of Cerebrolysin in tissue culture models of brain ischemia: post lesion application indicates a wide therapeutic window.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=10847556 Hartbauer M.nih.ncbi.gov/entrez/query.nlm. Hutter-Paier B.nih. In vitro models of brain ischemia: the peptidergic drug cerebrolysin protects cultured chick cortical neurons from cell death. http://www. Doppler E.ncbi. 4:59-65. Windisch M.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=16362636 Riley C.nih.nlm. Bull Exp Biol Med. 153.nlm. J Neural Transm.nih. Shram SI. 113:103-10.nih. Patockova J.gov/entrez/query. A peptide preparation protects cells in organotypic brain slices against cell death after glutamate intoxication. 133:401-3. Hutter-Paie B and Windisch M (2001). 151. Neurotox Res.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11459078 Gutmann B. http://www. 107:145-57. Hutter-Paier B. http://www. 108:581-92.nih.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=15843866 . Wronski R.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=12124658 Schauer E. Skofitsch G.

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