Unformatted text preview: Eugene Yevstratov MD
http://myprofile.cos.com/eugenefox Pathogenesis of ischaemic brain injury Depolarization Biochemical cascade Reperfusion injury 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 Depolarization Biochemical cascade
Glutamate Glutamatergic receptors Calcium influx Nitric oxide Calpains Gelsolin Cell death/Apoptosis 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 Hallmark Ischaemic brain leukocyte infiltration Reperfusion injury Inflamatory cascade activation Released large amounts of OFR Proinflamatory cytokine expression Neutrophils activation Cerebral oedema The Ischemic penumbra Strategies for mitigating ischaemic brain injury Hypothermia Biochemical intervention Pharmacological intervention Modification of techniques or
mechanical devices 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 Biochemical Intervention Ingibitors of presynaotic glutamate release Inhibitors of postsynaptic glutamate release Monosialogangliosides Ca2+ channel blockers Nitric oxide synthase inhibitors Calpain inhibitors Gelsolinlike chemical agents Caspase inhibitors Pharmacological strategies Corticosteroids Free radical inhibition Cytokine inhibition Antiadhesion molecule antibodies Presy naptic Ca2+ channels
Ntype conotoxins Na+ Pyramidines chan : Lamotrigine nels Licensed for epilepsy BW1003C8 In vitro and in vivo 7 experiments BW In vitro and in vivo 619C87 experiments Studied clinically Lubeluzole; for stroke In vitro and in vivo Riluzole experiments Hypotension, Lifarizine cardiac sideeffects SNX 111 Hypotension Postsy naptic NMDA receptors Non Aptiganel CNS1102 (Cerestat) compe Dizoclipine MK801 titive
Hypotension, hallucinogenic Toxicity NPS 1506 Anaesthetic, blood pressure effects Dextrometho AHN649 Blood pressure rphan effects Licensed for Memantine Parkinsonism Remacemide FPL 12495 Clinical study with desglycine CABG Less toxic than MK801 Compe Selfote CGS 19755 titive l
Glycine Felba site mate Toxicity / psychomimetic
In vitro and in vivo experiments studies dCPP CW 554 Lic.for epilepsy, protects in vitro ZD9379 In vitro and in vivo experiments Licosti ACEA In vitro and in vivo nel 1021 experiments ACEA In vitro and in vivo 1031 experiments ACEA In vitro and in vivo 1416 experiments AMPA receptors NBQX GYKI 52466 YM 90 K In vitro and in vivo experiments In vitro and in vivo experiments In vitro and in vivo experiments In vitro and in vivo experiments Intracerebral haemorrhage Monosialogan gliosides GM1 Ca2+ channels Nimodi pine AT 877 In vitro and in vivo experiments Gelso Microfil Cytochal aments alacin D lin Cal pain
NO NO synthase In vitro and in vivo experiments CbzVal In vitro and in vivo PheH experiments MDL In vitro and in vivo 28,170 experiments 7 nitroin In vitro and in vivo dazole experiments TRIM In vitro and in vivo experiments 1400 W In vitro and in vivo experiments BN In vitro and in vivo 80933 experiments Reper Cytokine fusion inhibition Soluble TNF In vitro and in reseptor I vivo experiments TNF Mab In vitro and in vivo experiments Endo Antiadhesion thelium Free Lazeroids Tirilazad radicals 74006F molecules In vitro and in vivo experiments In clinical trials U101033E In vitro and in vivo experiments PBN In vitro and in vivo experiments studies Apop tosis Caspa zVAD ses FMK In vitro and in vivo experiments z DEVD.FMK In vitro and in vivo experiments Modification of techniques or mechanical devices SCP Selective Cerebral Perfusion The End
[email protected] [email protected] Eugene Yevstratov MD ICCC Anesthesiology Division BsAs.Argentina ...
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This note was uploaded on 02/23/2012 for the course PHARM 290 taught by Professor Staff during the Fall '10 term at Rutgers.
- Fall '10