Brain Protection
Ahmad N. Hamdy, MD
Objectives (IOLs)
1
Cerebral physiology
2 Explain cerebral ischemia
Strategies to protect the brain from
3 cerebral ischemia
4
Algorithm for brain protection
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
75-80ml /100gm/min
Subcortical
20ml /100gm/min
Cerebral Physiology
CMRO2 3 to 3.5 ml/100gm/min
Whole brain O2 consumption 50ml/min
(20% of total body O2 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)
Factors Influencing CBF
Chemical/Metabolic /Humoral






Cerebral metabolic rate
Anaesthetics
Temperature
PaCO2 (20-80 mmHg)
PaO2
Vasoactive drugs - Anaesthetics,Vasodilators,
Vasopressors
Myogenic / Autoregulation
 Blood viscosity
Neurogenic
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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
Pathophysiology
Cerebral Ischemia
GLOBAL
• Cardiac arrest
• Resp. Failure
• Shock
• Hypoglycemia
• Asphyxia
FOCAL
• Head injury
• Vascular
Stenosis
• Occlusion
• Spasm
Biochemical & Pathophysiological
changes
Inadequate blood flow
↓↓O2 delivery
Ischaemia
Excitotoxic
cell death
Apoptotic
cell death
Inflammation
Strategies for Brain Protection
CMRO2
Oxygen
Glucose
Specific
Strategies
CBF&CPP
Future concepts
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
CMRO2
Hypothermia
Anesthetics
Body Temperature
Hyper
Ischaemic Injury
Hypo
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 postischemic 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
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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.
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
↑ of EPO in CNS
↓glial markers
of cerebral
injury
(S 100)
↓ infarct
size &
improved
recovery
Astrocytes in ischaemic penumbra produces
EPO in mammalian brain
Stimulates protein
of repair
↓↓neural
excitotoxicity
Stimulates
neurogenesis &
angiogenesis
↓neural
apoptosis
↓inflammatoin
Magnesium
Membrane stabilizer
Suggested protective mechanism:
•
•
•
•
•
Reduction of presynaptic release of glutamate
Blockade of NMDA receptors
Smooth muscle relaxation
Improved mitochondrial Ca2+ buffering
Blockage of Ca2+ 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
Specific
• CCBs
• Na CBs
• NMDA
antagonist
Future
• NO
• Cerebral
preconditioning
• Apoptosis
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