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Anti-ischemic Effect of Curcumin in Rat Brain

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Neurochem Res (2008) 33:1036–1043
DOI 10.1007/s11064-007-9547-y
ORIGINAL PAPER
Anti-ischemic Effect of Curcumin in Rat Brain
Pradeep K. Shukla Æ Vinay K. Khanna Æ
Mohd. M. Ali Æ Mohd. Y. Khan Æ Rikhab C. Srimal
Accepted: 8 November 2007 / Published online: 18 January 2008
Ó Springer Science+Business Media, LLC 2007
Abstract Turmeric has been in use since ancient times as a
condiment and due to its medicinal properties. Curcumin, the
yellow colouring principle in turmeric, is polyphenolic and
major active constituent. Besides anti-inflammatory, throm-
bolytic and anticarcinogenic activities, curcumin also
possesses strong antioxidant property. In view of the novel
combination of properties, neuroprotective efficacy of cur-
cumin was studied in rat middle cerebral artery occlusion
(MCAO) model. Rats were subjected to 2 h of focal ischemia
followed by 72 h of reperfusion. They were pre-treated with
curcumin (100 mg/kg, po) for 5 days prior to MCAO and for
another 3 days after MCAO. The parameters studied were
behavioural, biochemical and histological. Treatment with
curcumin could significantly improve neurobehavioral per-
formance compared to untreated ischemic rats as judged by its
effect on rota-rod performance and grid walking. A significant
inhibition in lipid peroxidation and an increase in superoxide
dismutase (SOD) activity in corpus striatum and cerebral
cortex was observed following treatment with curcumin in
MCAO rats as compared to MCAO group. Intracellular cal-
cium levels were decreased following treatment with
curcumin in MCAO rats. Histologically, a reduction in the
infarct area from 33% to 24% was observed in MCAO rats
P. K. Shukla
V. K. Khanna (&)
Mohd. M. Ali
R. C. Srimal
Developmental Toxicology, Industrial Toxicology Research
Centre, PO Box 80, MG Marg, Lucknow 226 001, India
e-mail: vkkhanna1@gmail.com
Present Address:
P. K. Shukla
Department of Psychiatry and Behavioral Sciences,
Feinberg School of Medicine, Northwestern University,
Chicago, IL 60611, USA
Mohd. Y. Khan
Dr. B.R. Ambedkar University, Lucknow 226 014, India
123
treated with curcumin. The study demonstrates the protective
efficacy of curcumin in rat MCAO model.
Keywords Curcumin
Middle cerebral artery occlusion

Neuroprotection
Oxidative stress
Introduction
It is largely accepted that stroke is a leading cause of
morbidity and poses serious health problems globally. The
affected persons often suffer from neurological deficits and
at times lead a crippled life [1]. Middle cerebral artery
occlusion (MCAO) in rat is widely used to study experi-
mental ischemic stroke and has provided invaluable
understanding of the patho-physiology of focal cerebral
ischemia. Several mechanisms have been suggested to be
involved in the etiology of stroke including NMDA
receptor activation leading to excitotoxicity, excessive
nitric oxide (NO) generation and free radical mediated
oxidative stress [2–4]. Recently, role of intercellular
adhesion molecule-1 (ICAM-1) protein has been suggested
in stroke since inhibition of ICAM-1 protein was found to
be neuroprotective in MCAO rats [5]. Several studies have
revealed that during ischemia there is excessive generation
of free radicals and the antioxidant defence is impaired
causing more vulnerability and damage to the brain [6].
A number of agents, both synthetic and natural, have
been screened to evaluate their preventive and therapeutic
efficacy against ischemia [7–10]. Dietary supplementation
with blueberries, spinach and spirulina reduces ischemia/
reperfusion induced apoptosis and cerebral infarction [6].
Turmeric (Curcuma longa rhizomes) has been extensively
used as an effective therapeutic agent since ages [11–14].
Turmeric as well as its constituent curcumin has been
Neurochem Res (2008) 33:1036–1043
shown to exhibit anti-inflammatory, anti-carcinogenic and
antioxidant activities, besides several other pharmacologi-
cal properties [15–21]. Prophylactic/therapeutic effect of
curcumin in cancer chemo-prevention, multiple sclerosis,
myocardial infarction etc. has been reported [22]. Curcu-
min has been found to be effective in the treatment of
anterior uveitis and cystic fibrosis [23, 24]. More recently,
neuroprotective efficacy of curcumin in attenuating 3-ni-
tropropionic acid (a fungal toxin) and lead induced
neurotoxicity has been reported [25, 26]. Pari and Murugan
found that tetrahydrocurcumin prevented brain lipid per-
oxidation in streptazotacin induced diabetic rats [27]. The
neuroprotective effect of curcumin was associated with its
anti-oxidant potential in these studies [27]. Curcumin has
been reported to cross the blood brain barrier [28] and
based on the potential of curcumin to inhibit formation of
amyloid beta oligomers and fibrils in mice use of curcumin
has been recommended for the clinical trials to prevent or
treat Alzheimer’s disease [28] Effect of curcumin was
studied in rats following intraperitoneal treatment, 30 min
after MCAO, indicating its neuroprotective potential in
ischemia. It has been suggested to be mediated through its
antioxidant activity [29] Our pilot studies conducted earlier
suggested that oral treatment with curcumin is also neu-
roprotective in ischemic rats [30]. Curcumin is recognised
as a promising compound with multiple pharmacological
properties and the present study was undertaken in rats
treated with oral curcumin before and after MCAO to
evaluate its neuroprotective efficacy.
Materials and methods
Animals
Male Wistar albino rats weighing 275–300 g from Industrial
Toxicology Research Centre animal breeding colony were
used in all the experiments. The animals were housed in
polypropylene cages in standard animal house conditions
and were fed pellet diet (Hindustan Lever Ltd. India) and
water ad libitum. Body weight of each animal was recorded
before and after the treatment. The study was approved by
the institutional ethics committee. The animals were divided
into three groups of 30 each as given below:
1. Sham operated
2. Middle cerebral artery occlusion (MCAO)
3. Curcumin treatment and MCAO
Experimental model of middle cerebral artery occlusion
Focal cerebral ischemia was induced following the stan-
dard procedure [31]. Briefly, the right common carotid
1037
artery of pentobarbitone anaesthetised (50 mg/kg, ip) rat
was exposed through a midline incision in the neck under
the operating microscope. A 4-0 nylon suture, the tip of
which was rounded by heating over the flame, was intro-
duced into the right external carotid artery and advanced
into the internal carotid artery for a length of 16 mm from
the bifurcation. The tip of the suture was placed at the
origin of the anterior cerebral artery, thereby occluding the
middle cerebral artery. The suture was left as such for 2 h.
The animal was allowed to recover from the anaesthesia
after closure of the operation site and the suture was gently
removed 2 h after MCAO.
Neurological score
Neurological evaluation of rats was carried out after
30 min to verify successful MCAO and immediately before
they were sacrificed after 72 h. An eight point behavioural
rating scale, modified from the scale as described by
Rogers et al. [1] was used to score the neurological deficits.
0 = no neurological deficit.
1 = failure to extend right forepaw fully.
2 = decreased grip of the right forelimb while tail gently
pulled.
3 = spontaneous movement in all direction, contralat-
eral circling only if pulled by the tail.
4 = circling or walking to the right.
5 = walks only when stimulated.
6 = unresponsive to stimulation with a depressed level
of consciousness.
7 = dead.
Treatment
Curcumin from rhizomes of Curcuma longa (suspended in
2% gum acacia) was used to investigate its protective
potential against MCAO. Rats were pre-treated with cur-
cumin (100 mg/kg, po) for 5 days before MCAO. The
treatment was continued for another 3 days after MCAO
following which behavioural, biochemical and histological
studies were carried out.
Behavioural studies
(i) Rota-Rod performance: Rats were conditioned to the
accelerating rota-rod before MCAO. Each animal
received training on the rota-rod (rotating at a constant
speed of 8 rpm) and was trained until it achieved a
criterion of staying on the rod for 60 s. The rats then
123
1038
received single baseline training on the rota-rod in
which the speed was increased from 4 to 40 rpm over
a period of 5 min. At 24-h post occlusion, each rat
received another trial on the rota-rod and scoring was
carried out by a person blind to the condition [1].
(ii) Grid walking: Rats were acclimatised for 1 min to an
elevated level of stainless steel grid with mesh size of
30 mm before MCAO. At 24-h post-occlusion, they
were placed on the grid again for 1 min and the total
number of paired steps (placement of both fore limbs)
were counted. The scoring was carried out by a
person blind to the condition. Foot-fault error (in
which the animal made mistake in placing the
forelimbs or it fell from the grid) was monitored
and the total number of errors in placing the forelimbs
was recorded [1].
Biochemical estimations
Rats in all groups were sacrificed 72 h after MCAO by
cervical decapitation and the brains were immediately
removed. The brain regions, corpus striatum and cerebral
cortex, were dissected out following the standard procedure
[32] and processed for biochemical assays within 45 min in
each case.
(i) Lipid peroxidation: As a measure of lipid peroxida-
tion, malonaldialdehyde (MDA) levels were estimated
by measuring thiobarbituric acid reactive substances
(TBARS) following the standard protocol [33].
Briefly, equal volumes (120 ll) of EDTA (10 mM),
ascorbate (10 mM) and mixture of EDTA (16.7 mM)
and FeSO4 (16.7 mM) were mixed and to this
homogenate of different brain regions (0.6 ml) was
added. The reaction mixture was incubated at 37°C for
0 and 60 min. Immediately after incubation, the
reaction was stopped by adding 1 ml of ice cold
10% trichloro acetic acid (TCA). The deproteinised
homogenate was centrifuged at 2000g for 10 min and
supernatant was aspirated out. The supernatant was
mixed with an equal amount of 0.67% TBA and kept
in boiling water bath for 15–20 min. The intensity of
pink colour developed was read at 532 nm on a
spectrophotometer.
(ii) Superoxide dismutase: Activity of superoxide dismu-
tase (SOD) was measured following the method of
Kakkar et al. [34] using NADH as a substrate.
Briefly, the assay mixture in a final volume of 3 ml
contained sodium pyrophosphate buffer (0.082 M,
pH 8.3), phenazine methosulphate (186 lM), nitro
blue tetrazolium (300 lM), NADH (780 lM),
enzyme preparation and distilled water. The reaction
123
Neurochem Res (2008) 33:1036–1043
was started by the addition of NADH followed by
incubation at 37°C for 90 s. The reaction was stopped
by adding 1 ml of glacial acetic acid and the reaction
mixture was vigorously shaken with 4 ml of n-
butanol. The mixture was allowed to stand for
10 min, centrifuged and butanol layer was separated.
The colour intensity of the chromogen in butanol was
measured at 560 nm against butanol using a spectro-
photometer. A mixture without enzyme preparation
was run in parallel to serve as control. The SOD
activity was expressed as units/mg protein. One unit
of the enzyme was the amount required to inhibit the
rate of chromogen formation by 50%.
(iii) Intracellular calcium: The levels of intracellular
calcium were determined fluorometrically using
Quin-2AM as a fluorescent dye following the method
of Komulainen and Bondy [35]. Briefly, synapto-
somes containing 150–250 mg protein were incubated
in 3 ml Hepes buffer (25 mM Hepes, 12 mM NaCl,
5 mM KCl, 1.2 mM MgSO4, 6 mM glucose, 6 mM
CaCl2, 5 mM NaHCO3, pH 7.4) with fluoremetric dye
Quin–2AM at a final concentration of 25 lM for
45 min in dark at 37°C. After the incubation was over,
the assay mixture was centrifuged at 34,000g for
15 min. To remove unbound Quin–2AM, the pellet
was carefully washed twice with assay buffer and
centrifuged at the same speed for same time. Finally,
pellet was suspended in 2 ml assay buffer. The emit-
ted fluorescence of the sample was recorded on a
spectrophotofluorometer at excitation/emission 339/
492 nm respectively. Extracellular calcium was
quenched by adding MnCl2 (40 lM) and the fluores-
cence R was measured. Fluorescence R minimum was
recorded after addition of sodium dodecyl sulphate
(0.1%) and alkaline EGTA (5 mM) while R maximum
was determined by addition of CaCl2 (7 mM) and
intracellular calcium levels were calculated using the
formula,
[Ca]i ¼ Kd (R - Rmin )/(Rmax - R)
Kd = 115 nM is the dissociation constant of Quin-
2AM complex
(iv) Protein estimation: Protein content was measured
following the method of Lowry et al. using bovine
serum albumin as a reference standard [36].
Histological studies
Five coronal sections (2 mm thick) of the whole brain were
taken from the region beginning 1 mm from the frontal pole
Neurochem Res (2008) 33:1036–1043 1039

and ending just rostral to the cortico-cerebellar junction and Table 2 Protective effect of curcumin on rota-rod performance in
stained with 2% 2,3,5-triphenyl tetrazolium chloride [4]. The rats subjected to middle cerebral artery occlusion for 2 and 72 h after
ischemic reperfusion injury
damage following MCAO and any protection with curcumin
was assessed by an image analysis software. Group Time of fall (s)

Sham 215 ± 34
Statistical analysis Ischemic (MCAO) 77 ± 17*
Curcumin pre-treated ischemic 165 ± 15**
Data were analysed by comparing the mean ± SE of each Values are mean ± standard error of eight animals in each group
group and subjected to Student’s t test and P \ 0.05 was * Significantly differs from sham (P \ 0.05)
considered significant. ** Significantly differs from ischemic (MCAO) group (P \ 0.05)

Results compared to sham, suggesting an impairment in the

rota-rod performance. Treatment with curcumin in
Body weight MCAO rats resulted in a significant protection, as
evident by an increase in the time of fall in compar-
A significant decrease in body weight was observed in ison to ischemic (MCAO) rats (Table 2).
ischemic rats, 72 h after MCAO. However, a marginal (ii) Grid walking: A significant impairment in grid
change in body weight was observed in sham group walking was observed following MCAO. These rats
(Table 1). Treatment of rats with curcumin showed an exhibited a decrease in total steps covered/minute and
insignificant fall in body weight. also showed error in placement of fore limbs during
the grid walking test as compared to sham. Treatment
with curcumin in ischemic rats caused a significant
Neurological score protection both in the total number of steps covered/
minute and errors in placement of fore limbs
Rats exhibited focal neurological deficits following MCAO (Table 3).
with failure to fully extend the forepaw. Forty percent rats
died within 24 h due to severe brain infarction. No neu-
rological deficit was observed in sham-operated animals. Biochemical changes
Treatment with curcumin showed a significant decrease in
neurological score (range from 0 to 7), (Table 1). (i) Effect on lipid peroxidation: A significant increase in
malonaldialdehyde level was observed in corpus stri-
atum (100%) and cortex (66%), 72 h after MCAO.
Behavioural changes Treatment with curcumin significantly decreased the
MDA levels both in corpus striatum and cortex as
(i) Rota-Rod performance: The time of fall from the rod compared to ischemic group (Fig. 1).
was significantly decreased, 72 h after MCAO as (ii) Effect on superoxide dismutase activity: Activity of
superoxide dismutase was significantly decreased in
Table 1 Effect of curcumin on body weight and neurological score
in rats subjected to middle cerebral artery occlusion for 2 and 72 h ischemic rats, both in the corpus striatum (52%) and
after ischemic reperfusion injury
Group Initial Post-treatment Neurological Range Table 3 Protective effect of curcumin on grid walking performance
weight (g) weight (g) scores in rats subjected to middle cerebral artery occlusion for 2 and 72 h
after ischemic reperfusion injury
Sham (n = 10) 295 ± 6.4 298 ± 2.3 0 0–0
Ischemic 311 ± 5.1 272 ± 4.3* 4.36 ± 0.7* 1–7 Group Total steps/60 s Errors in placement of
(MCAO) forelimb
(n = 6)
Sham 35 ± 2.5 1 ± 0.4
Curcumin 305 ± 10 296 ± 2.3 1.90 ± 0.7** 0–7
pre-treated Ischemic (MCAO) 17 ± 1.7* 5 ± 0.8*
ischemic Curcumin pre-treated 26 ± 1.1** 3 ± 0.4**
(n = 8) ischemic
Note: n represents the number of animals in each group Values are mean ± standard error of eight animals in each group
* Significantly differs from sham (P \ 0.05) * Significantly differs from sham (P \ 0.05)
** Significantly differs from ischemic (MCAO) group (P \ 0.05) ** Significantly differs from ischemic (MCAO) group (P \ 0.05)

123
1040
Fig. 1 Protective effect of curcumin on lipid peroxidation in rats
subjected to middle cerebral artery occlusion for 2 and 72 h after
ischemic reperfusion injury. Values are mean ± SE of eight rats in
each group. a—significantly differs from sham; b—significantly
differs from ischemic group. * P \ 0.05, ** P \ 0.01
cortex (33%) as compared to sham. Activity of the
enzyme was significantly increased following treat-
ment with curcumin in both brain regions as
compared to ischemic rats (Fig. 2).
(iii) Effect on intracellular calcium: Intracellular calcium
levels were significantly elevated in the ischemic rats
both in corpus striatum (97%) and cortex (137%) as
compared to sham. Treatment with curcumin in
MCAO group significantly decreased the intracellu-
lar calcium levels in both the regions compared to
ischemic rats (Fig. 3).
Ischemic damage
In ischemic rats, contralateral hemispheric infarction was
well demarcated (33%), 72 h after MCAO, as revealed by
Fig. 2 Protective effect of curcumin on superoxide dismutase
activity in rats subjected to middle cerebral artery occlusion for 2
and 72 h after ischemic reperfusion injury. Values are mean ± SE of
eight rats in each group. a—significantly differs from sham; b—
significantly differs from ischemic group. * P \ 0.05, ** P \ 0.01
123
Neurochem Res (2008) 33:1036–1043
Fig. 3 Protective effect of curcumin on intracellular calcium levels
in rats subjected to middle cerebral artery occlusion for 2 and 72 h
after ischemic reperfusion injury. Values are mean ± SE of eight rats
in each group. a—significantly differs from sham; b—significantly
differs from ischemic group. * P \ 0.05, ** P \ 0.01
histological analysis of the brain. Interestingly, treatment
with curcumin in ischemic rats resulted in only 24% con-
tralateral hemispheric infarction. No ischemic damage was
noticed in brain sections of the sham operated rats (Fig. 4).
Discussion
An impairment in the sensorimotor functions is well known
following ischemia. In the present study, the neurological
score was found to be increased due to ischemic damage.
Treatment with curcumin resulted in significant decrease in
the neurological score. Neurological score was also co-
related with severity of infarction [1]. Grid walking is one
of the sensitive tests to monitor the spontaneous locomotor
activity and muscle co-ordination. Any deficit in placement
of forelimbs and foot-fault error is easily detected through
grid walking test. Rats with ischemic reperfusion injury
following transient and permanent occlusion of middle
cerebral artery have been reported to show an impairment
in grid walking [1]. Errors in placement of foot and
40
35
30
% change
25
20
15
10
5
0
Sham MCAO MCAO+Curcumin
Fig. 4 Protective effect of curcumin on percent of infarcted area in
rats subjected to middle cerebral artery occlusion for 2 and 72 h after
ischemic reperfusion injury. Histological infarction in rat brain
coronal sections after staining with TTC in MCAO rats and those
treated with curcumin. Values are represented in % after taking
average of five animals in each group
Neurochem Res (2008) 33:1036–1043
impaired co-ordination following MCAO for 2 h was also
observed in the present study. Rota-rod performance was
affected following MCAO in rats, which provided another
evidence of impaired balance and muscle co-ordination due
to ischemic-reperfusion injury. It has been reported that
rota-rod performance in the rats is significantly affected
following focal cerebral ischemia [37]. A linear relation-
ship between the duration of ischemia and time during
which rats stay on the accelerating rod has been reported.
Significantly, treatment with curcumin in the MCAO rats
caused an improvement in the grid walking and co-ordi-
nation as evident by the score of foot fault errors. The time
of fall from the rotating rod was also significantly increased
in these animals suggesting that curcumin treatment could
significantly prevent impairment of sensorimotor functions.
Further, a significant improvement in neurological score
following curcumin treatment, observed in the present
study, is quite interesting and is consistent with the above
findings.
A number of studies have observed that both cortex and
corpus striatum are affected following stroke [38]. The rea-
son for including corpus striatum in the present study was
also due to the fact that motor functions are severely affected
following ischemia [1]. We have studied gross neuropro-
tective effects of curcumin without going into details of the
mechanisms at cellular or molecular levels. Enhanced oxi-
dative stress due to increased generation of free radicals has
been reported during cerebral ischemia [9, 37, 39]. An
increase in the levels of oxygen and hydroxyl radicals fol-
lowing MCAO has also been shown. However, free radical
generation is enhanced more during reperfusion [37].
Kuroda et al. suggested that generation of free radical species
is an important contributor to brain damage [40]. An increase
in lipid peroxidation and a decrease in superoxide dismutase
activity in corpus striatum and cortex, 72 h after MCAO
observed in the present study suggest a state of enhanced
oxidative stress. Protective effect of curcumin against cere-
bral ischemia in rats has been studied by Thiyagarajan and
Sharma [29]. They attributed the neuroprotective effect of
curcumin to its anti-oxidant property. However, a different
route and schedule of curcumin administration was used in
these studies. We have used a more clinically relevant route
of administration.
A decrease in body weight following MCAO, observed
in the present study, is consistent with the earlier reports of
post-ischemic loss in body weight [1, 37]. Garcia and Liu
reported that the body weight decrease was probably due to
infarction affecting feeding behaviour and injury to the
anterior hypothalamus [41]. The decrease in body weight in
ischemic rats in the present study could be due to decreased
food intake of these rats.
Since multi-factorial mechanisms are involved in
ischemia, a number of synthetic and natural agents have
1041
been used to investigate their protective and therapeutic
efficacy [9, 42]. Vitamin B3, Vitamin E, NMDA receptor
antagonists, Na+ channel blockers and Nitric oxide syn-
thase (NOS) inhibitors have been used and found effective
in the experimental model of MCAO [3, 10, 43]. Use of
herbal products in the management of ischemia has also
been advocated because of their high antioxidant activity
[9, 42]. Dietary supplementation with blueberries, spinach
and spirulina have been reported to reduce ischemia/
reperfusion induced apoptosis and cerebral infarction [6]. It
has been observed that agents that inhibit lipid peroxidation
or have strong antioxidant activity are useful in the treat-
ment of this disease [9, 42, 44]. In an interesting study by
Chabrier et al. BN 80933, a dual inhibitor of lipid perox-
idation and NOS, significantly protected rats from ischemia
in different experimental models [3].
Curcumin, an important ingredient of turmeric, is a
cyclooxygenase inhibitor and possesses multiple pharma-
cological properties including anti-inflammatory, anti-
carcinogenic and anti-thrombotic [18, 45]. These properties
of curcumin might have also contributed to its anti-ischemic
efficacy but it is difficult to confirm them in the present study.
Free radical scavenging activity of curcumin and its pro-
tective effect against reactive species is well documented
[46]. Curcumin is unique over other natural antioxidants
since it possesses both the phenolic and diketonic groups
which help in the scavenging of free radicals. In contrast,
other natural antioxidants possess either phenolic or dike-
tonic groups [47]. Curcumin has been found to be
neuroprotective against different neurotoxicants [48, 49].
One of the characteristic property of curcumin is that it does
not affect the normal cells. In our earlier studies investigating
the neuroprotective efficacy of curcumin against lead
neurotoxicity, treatment of rats only with curcumin (100 mg/
kg, po) for 45 days had no significant effect on parameters
related with behaviour and oxidative stress [49].
Treatment of ischemic rats with curcumin significantly
inhibited lipid peroxidation both in corpus striatum and
cortex in the present study. Thiyagrajan and Sharma also
observed inhibition in lipid peroxidation following intra-
peritoneal treatment with curcumin [29]. Effect was more
marked at a higher dose (300 mg/kg) of curcumin.
Absorption of curcumin in the body may occur both by
gavage and intraperitoneal routes although bioavailability
and pharmacokinetic properties are different [50]. Oral
administration of curcumin has been reported to inhibit
lipid peroxidation induced by carbon tetrachloride, parquat
and cyclophosphamide in brain, kidney, liver and lung in
mice [48]. It is, however, not clear whether inhibition in
lipid peroxidation is due to scavenging of peroxides and
toxic free radical species generated during the reaction or
neutralisation of free radicals [48]. As curcumin has xan-
thine oxidase inhibitory activity [51], it may prevent
123
1042
production of superoxide during ischemia. Curcumin has
been reported to cross the blood-brain barrier in aged mice
and its use recommended in the treatment/prevention of
Alzheimer’s disease [28]. In another study on gerbils, it
was suggested that polyphenol enriched curcumin may
cross the blood-brain barrier [52]. The anti-oxidant effect
of curcumin in the present study may be attributed due to
blood-brain barrier permeability.
Sharma et al. in an interesting study, reported that cur-
cumin inhibited the formation of lipid peroxides even in the
presence of agents that induced lipid peroxidation sug-
gesting its strong antioxidant property [53]. In the present
study, treatment with curcumin increased the superoxide
dismutase activity in ischemic rats, which further provides
an evidence of its antioxidant potential.
Role of intracellular calcium in ischemic damage and
protective effect of calcium channel blockers in ischemia has
been suggested [43]. Obstruction of cerebral vessels in
cerebral stroke has been accepted to cause decreased cerebral
blood flow and ATP associated with energy loss [54]. As a
result, the ionic gradients across the membranes are affected.
Efflux of K+ from cells producing cellular depolarisation and
the movement of extracellular calcium into cells through
calcium channels are physiological consequences. An
increase in intracellular calcium enhances break down of
phospholipids, proteins and nucleic acids and thus linked
with calcium toxicity in cerebral ischemia [54]. Recently,
Matteucci et al. found that curcumin treatment protected rat
retinal neurons against excitotoxicity by decreasing the
intracellular calcium levels modulated by NMDA receptors
[55]. An increase in intracellular calcium level following
MCAO and its inhibition following curcumin treatment in
ischemic rats is interesting. It is, however, difficult to com-
ment whether such an effect is due to formation of any
complex or blocking of calcium channels.
Low mortality in ischemic rats treated with curcumin
(around 10%) as compared to ischemic rats (40%) suggest
that curcumin may affect the mortality in ischemia by
providing protection. Although a reduction in the severity
of infarction was observed in ischemic rats treated with
curcumin, the effect was not as striking as observed in
behavioural and biochemical parameters. It is possible that
treatment with curcumin for more time and/or at higher
dose might be more effective on the infarct size but that
needs further study. The present dose and duration were
based on literature reports. The study, however, does pro-
vide an evidence of the protective effect of curcumin
against ischemia in rats.
Acknowledgements The study was supported by a grant from the
Council of Scientific and Industrial Research, New Delhi. The authors
acknowledge the technical assistance of M/S. Kanhiya Lal and
Buddhi Sagar Pandey.
123
Neurochem Res (2008) 33:1036–1043
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