Brain

Protection
Ahmad N. Hamdy, MD
Objectives (IOLs)
Cerebral physiology 1
Explain cerebral ischemia
2
3
Algorithm for brain protection
4
Strategies to protect the brain from
cerebral ischemia
Cerebral Physiology
BRAIN 1350 gm- 2% of total adult body wt
Receives 12 to 15 % of cardiac output
Global cerebral blood flow 45-55ml/100
gm / min


Cortical Subcortical
75-80ml /100gm/min 20ml /100gm/min
CMRO
2
3 to 3.5 ml/100gm/min
Whole brain O
2
consumption 50ml/min
(20% of total body O
2
consumption)
Cerebral glucose utilization 5.5 gm/100gm
of brain tissue (1ry energy source)
ICP ( supine) 5 to 15 mm Hg
CPP= MAP- ICP or (CVP), whichever is
greater (90-100 mm Hg)
Cerebral Physiology
Factors Influencing CBF
Chemical/Metabolic /Humoral
Cerebral metabolic rate
Anaesthetics
Temperature
PaCO
2
(20-80 mmHg)
PaO
2

Vasoactive drugs - Anaesthetics,Vasodilators,
Vasopressors
Myogenic / Autoregulation
Blood viscosity
Neurogenic
Cerebral Ischemia
It is the potentially reversible
altered state of brain physiology and
biochemistry that occurs when
substrate delivery is cut off or
substantially reduced by vascular
stenosis or occlusion

Metabolic demands > substrate delivery

Company Logo
Pathophysiology
GLOBAL
Cardiac arrest
Resp. Failure
Shock
Hypoglycemia
Asphyxia





Cerebral Ischemia
FOCAL
Head injury
Vascular
Stenosis
Occlusion
Spasm
Biochemical & Pathophysiological
changes

Inadequate blood flow

O
2
delivery

Ischaemia


Excitotoxic Apoptotic Inflammation
cell death cell death

Strategies for Brain Protection
Strategies
CMRO2
Oxygen
CBF&CPP
Future concepts
Glucose
Specific
Oxygen & Glucose
In the absence of oxygen, glucose
undergoes anaerobic glycolysis resulting
in intracellular acidosis
Patients with higher blood glucose concentrations have
worse outcomes from stroke, TBI, etc.
More rapid expansion of ischemic lesion in
hyperglycemic, compared with normoglycemic patients
For all of this reasons, it is rational to
maintain normoglycemia in all patients at
risk for ,or recovering from acute brain
injury
CMRO
2

Hypothermia
Anesthetics
Body Temperature



Hyper Hypo
Ischaemic Injury
Temperature
Hypothermia
Reduce CMR in a temperature-dependent fashion
Mild hypothermia(32-35) ; negliable effect on CMR
But, in several studies mild hypothermia produce major
protection ; provides scientific basis of using off-bypass
hypothermia to provide meaningful neuroprotection
Deep hypothermia(18-22) ; highly neuroprotective
In normothermic brain ; only a few minutes of complete global
ischemia cause neuronal death
In deep hypothermia before circulatory arrest ; brain can tolerate
over 40 min and completely or near-completely recover
Temperature
Hyperthermia
In animal studies, spontaneous post-
ischemic hyperthermia is common and intra-
ischemic or even delayed post-ischemic
hyperthermia dramatically worsen outcome
Advocate frequent temperature monitoring in
patients with cerebral injuy
Aggressive treatment of hyperthermia should
be considered
Anesthetics
Volatile anesthetics
Protect against both focal and global ischemia
Transient improvement in global ischemia
Persistent improvement in focal ischemia
Suppression of energy requirements
Inhibition of excitatory neurotransmission
Potentiation of inhibitory receptors
Regulation of intracellular calcium response during ischemia
Isoflurane, sevoflurane ;
Desflurane ; insufficiently studied
Anesthetics
Barbiturates have major actions on CNS:
hypnosis
depression of CMR
anticonvulsant activity.
These properties make barbiturates,
particularly thiopental, the most
commonly used induction agents in
neuroanesthesia.
Company Logo
Anesthetics
Propofol
Suppression of CMR
Free radical scavenging
Anti-inflammatory properties
Appears efficacy similar to barbiturates
Etomidate
Paradoxically exacerbate ischemic injury
Cannot use for neuroprotection
Lidocaine
Suppress CMR
Inhibition of apoptosis
No long-term outcome studies
Ketamine
Inhibition of glutamate at NMDA receptor
Little or no protection against global insult
Substantial protection against focal insult
However, no human data
CPP
More than 65-70mmHg
Elevation of MAP
Decrease ICP
Decrease blood viscosity
Specific
CCBs as nimodipine (SAH)
Na CBs as lamotrigine (SDH)
NMDA antagonist
Steroids (Brain tumors)
Preconditioning

Ischaemic Preconditioning

Homeothermic mammal

Elicits an evolutionary conserved
endogenous response to decreased
blood flow and oxygen limitation such
as seen during hibernation

Clinical methods of preconditioning
Pre - op hyperbaric oxygen
Normobaric 100 % oxygen
Electroconvulsive shock
K
+
channel opener Diazoxide
Erythropoietin (EPO)


Erythropoietin
Cytokine growth hormone
- apoptosis
- erythrocyte production
haematocrit

Deleterious effect on ischaemia




Intravenous recombinant erythropoietin
Once daily for 3 days




60 -100 fold glial markers infarct
of EPO in CNS of cerebral size &
injury improved
(S 100) recovery


Astrocytes in ischaemic penumbra produces
EPO in mammalian brain





Stimulates protein Stimulates
of repair neurogenesis &
angiogenesis



neural
apoptosis
neural inflammatoin
excitotoxicity
Magnesium
Membrane stabilizer
Suggested protective mechanism:
Reduction of presynaptic release of glutamate
Blockade of NMDA receptors
Smooth muscle relaxation
Improved mitochondrial Ca
2+
buffering
Blockage of Ca
2+
entry
Protection depends on:
Time of treatment initiation
Type of cerebral ischemia
Benefit in neocortical stroke
Strategies for Brain Protection
O2
HCT: 30-34
%
PaO2 Levels
GL.
100- 150
mg/dl
CMRO2
Hypothermia
Anesthetics
Strategies of Brain Protection (Cont.)
CBF
CPP: 70 mmhg
MBP: Elevated
Viscosity:
Decresed
ICP: Decrease
Future
NO
Cerebral
preconditioning
Apoptosis
Specific
CCBs
Na CBs
NMDA
antagonist
Thank You !
Add your company slogan