[Regulatory mechanisms in focal cerebral ischemia. New possibilities in neuroprotective therapy].
Permanent or temporary disruption of cerebral blood flow rapidly depletes brain regions of their limited energy reserves (glycogen, glucose, oxygen, ATP) leading to an energy crisis. Tissue damage occurs due to the energy crisis. The central part of the damage, the ischaemic "core" region is surrounded by zones of the shell-like penumbra. Necrotic, as well as apoptotic cell death could be identified in the penumbra. Going away from the ischaemic core different neurochemical processes are occurring by space and time. "Immediate early response" genes (c-fos, fos-B, c-Jun, krox 20, 24) are activated, heatshock proteins (hsp 70, 72, HSF, HSE, HIF), cytokines (TNF-alpha, IL-1 beta), inflammatory factors (COX), adhesion and glial factors (ICAM-1, ELAM-1, P-selectin), vasoactive factors (IL-6, -10, PAF), reactive oxigen radicals and connected factors (O2, OH, NO, NOS, SOD) are produced within minutes and hours. Cell deaths, necrosis and apoptosis due to the activation of calpains, caspases and nucleases occur in days. In parallel, growth factors and plasticity proteins (BDNF, NGF, TGF-beta, VEGF, PDGF, GAP-43) are activated as a basis of functional rehabilitation.
Nagy
Zoltán
Z
Agyérbetegségek Országos Központja, Semmelweis Egyetem, Vascularis Neurológiai Tanszék, Budapest. stroke@opni.hu
Simon
László
L
Bori
Zoltán
Z
D017209:Apoptosis / Q000235:genetics; D030161:Avian Proteins; D001921:Brain / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002560:Cerebrovascular Circulation; D016207:Cytokines / Q000378:metabolism; D015316:Genetic Therapy; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009336:Necrosis; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D014666:Vasomotor System / Q000378:metabolism
D030161:Avian Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; C410845:ERNI protein, chicken; D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D002118:Calcium