[Apoptosis in focal brain ischemia]

Ideggyogy Sz. 2003 Jul 20;56(7-8):216-28.
[Article in Hu]

Abstract

Ischaemic stroke is one of the major causes of death and disability in the developed world. It is caused by focal impairment of cerebral blood flow. The subsequent ischaemic cell death is predominantly necrotic in nature. However, a therapeutically important characteristic is the delayed apoptotic cell demise in the border zone of the primary lesion core. Apoptosis is one of the most intensively studied field of current medical and biological research. The better understanding of its mechanism may provide novel and more effective ways of therapy in a wide range of diseases including ischemic stroke. The salient neurological features of focal brain ischaemia and the morphological signs of apoptotic and necrotic cell death are summarized. The mechanism of apoptosis is discussed. It is divided into an early genetic phase of decision-making followed by a cellular execution phase. The characteristics of the early shift in the finely tuned balance of pro- and antiapoptotic genes and their protein products, which is preceded by an inbalance in intracellular ionized calcium homeostasis, energy depletion and mitochondrial dysfunction is discussed. The crucial role of caspases in apoptosis is emphasized. The three possible pathways during the execution phase is described: the intrinsic- and extrinsic caspase activation cascade and the caspase-independent intracellular signal transduction route. The molecular mechanism of neural cell membrane damage in the execution phase is discussed and some examples of altered protein synthesis also known as message-selection are given. The important role of late reperfusion in the execution phase is emphasized. The possible targets of antiapoptotic therapeutic approaches and the results of experimental studies are presented as well as the perspectives of their use in human clinical care.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Apoptosis*
  • Brain Infarction* / etiology
  • Brain Infarction* / metabolism
  • Brain Infarction* / pathology
  • Brain Infarction* / physiopathology
  • Brain Ischemia* / complications
  • Brain Ischemia* / metabolism
  • Brain Ischemia* / pathology
  • Brain Ischemia* / physiopathology
  • Calcium Channels / metabolism
  • Caspases / metabolism
  • Cerebrovascular Circulation
  • Humans
  • Necrosis
  • Signal Transduction

Substances

  • Calcium Channels
  • Caspases