Presentaci

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Eugene Yevstratov MD
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Pathogenesis of ischaemic brain injury

• Depolarization
• Biochemical cascade
• Reperfusion injury

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Depolarization
Cessation of neuronal electrical ativity Energy
loss Impair ion homeostasis Depletion of high
energy phosphates Membrane ion pump
failure Efflux of cellular K Influx of Na ,Cl and
H2O
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Biochemical cascade
Glutamate Glutamatergic receptors Calcium
influx Nitric oxide Calpains Gelsolin Cell
death/Apoptosis
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Evidence for a role of Glutamate in Ischemic
Neuronal Injury

• High concentrations of Glutamte receptors occur
  in seletively vulnerable neurons
• High concentrations of Glutamateare released in
  ischemic brain regions
• Lesioning of glutamergic pathways reduces
  ischemic injury
• NMDA or AMPA receptors blockade reduces ischemic
  injury
• Delayed Ca2 overload occurs in selectively
  vulnerable neurons, which is not blocked by Ca2
  channel blockers

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Reperfusion injury
Hallmark Ischaemic brain leukocyte
infiltration Inflamatory cascade
activation Released large amounts of
OFR Proinflamatory cytokine expression Neutrophils
activation Cerebral oedema
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Strategies for mitigating ischaemic brain injury

• Hypothermia
• Biochemical intervention
• Pharmacological intervention
• Modification of techniques or mechanical devices

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Hypothermia(HCA)
Mild systemic hypotermia 34Co Mild to moderade
hypotermia 34 30 Co Moderade Hypotermia 30 28
Co Severe Hypotermia 28 18 Co Profound
Hypotermia 18 15 Co
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Biochemical Intervention

• Ingibitors of presynaotic glutamate release
• Inhibitors of postsynaptic glutamate release
• Monosialogangliosides
• Ca2 channel blockers
• Nitric oxide synthase inhibitors
• Calpain inhibitors
• Gelsolin-like chemical agents
• Caspase inhibitors

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Pharmacological strategies

• Corticosteroids
• Free radical inhibition
• Cytokine inhibition
• Anti-adhesion molecule antibodies

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Modification of techniques or mechanical devices
SCP Selective Cerebral Perfusion RCP Retrograde
Cerebral Perfusion
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The End

• ostlandfox_at_yahoo.de
• ostlandfox_at_medscape.com
• Eugene Yevstratov MD
• ICCC Anesthesiology Division
• BsAs.Argentina