Ischemic preconditioning: a novel target for neuroprotective therapy

Cerebrovasc Dis. 2006:21 Suppl 2:38-47. doi: 10.1159/000091702. Epub 2006 May 2.

Abstract

Ischemic preconditioning involves a brief exposure to ischemia in order to develop a tolerance to injurious effects of prolonged ischemia. The molecular mechanisms of neuroprotection that lead to ischemic tolerance are not yet completely understood. However, it seems that two distinct phases are involved. Firstly, a cellular defense function against ischemia may be developed by the mechanisms inherent to neurons such as posttranslational modification of proteins or expression of new proteins via a signal transduction system to the nucleus. Secondly, a stress response and synthesis of stress proteins (heat shock proteins) may be activated. These mechanisms are mediated by chaperones. The objective of ischemic preconditioning research is to identify the underlying endogenous protective cellular receptors and signaling cascades, with the long-term goal of allowing therapeutic augmentation of the endogenous protective mechanisms in cerebral ischemia and possibly development of new neuroprotective strategies for ischemic stroke treatment.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Brain / blood supply
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Brain Ischemia / therapy
  • Clinical Trials as Topic
  • Cytokines / metabolism
  • Diazoxide / pharmacology
  • Diazoxide / therapeutic use
  • Drug Evaluation, Preclinical
  • Gene Expression Regulation
  • Genes, Immediate-Early
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Ischemic Preconditioning* / methods
  • Models, Animal
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Potassium Channels / metabolism
  • Receptors, Glutamate / metabolism
  • Stroke / genetics
  • Stroke / metabolism*
  • Stroke / therapy
  • alpha-Linolenic Acid / pharmacology
  • alpha-Linolenic Acid / therapeutic use

Substances

  • Cytokines
  • Heat-Shock Proteins
  • Neuroprotective Agents
  • Potassium Channels
  • Receptors, Glutamate
  • alpha-Linolenic Acid
  • Adenosine Triphosphate
  • Diazoxide