Title: Presentacin de PowerPoint
1Eugene Yevstratov MD
2Pathogenesis of ischaemic brain injury
- Depolarization
- Biochemical cascade
- Reperfusion injury
3Depolarization
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
4Biochemical cascade
Glutamate Glutamatergic receptors Calcium
influx Nitric oxide Calpains Gelsolin Cell
death/Apoptosis
5Evidence 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
6Reperfusion 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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9Strategies for mitigating ischaemic brain injury
- Hypothermia
- Biochemical intervention
- Pharmacological intervention
- Modification of techniques or mechanical devices
10Hypothermia(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
11Biochemical 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
12Pharmacological strategies
- Corticosteroids
- Free radical inhibition
- Cytokine inhibition
- Anti-adhesion molecule antibodies
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21Modification of techniques or mechanical devices
SCP Selective Cerebral Perfusion RCP Retrograde
Cerebral Perfusion
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24The End
- ostlandfox_at_yahoo.de
- ostlandfox_at_medscape.com
- Eugene Yevstratov MD
- ICCC Anesthesiology Division
- BsAs.Argentina