Ischemic tolerance and endogenous neuroprotection

Trends Neurosci. 2003 May;26(5):248-54. doi: 10.1016/S0166-2236(03)00071-7.


Practically any stimulus capable of causing injury to a tissue or organ can, when applied close to (but below) the threshold of damage, activate endogenous protective mechanisms--thus potentially lessening the impact of subsequent, more severe stimuli. A sub-threshold ischemic insult applied to the brain, for example, activates certain cellular pathways that can help to reduce damage caused by subsequent ischemic episodes--a phenomenon known as 'ischemic preconditioning' (IP) or 'ischemic tolerance' (IT). Although investigated for some time in model organisms, IP/IT has recently been shown in human brain. This opens a window into endogenous neuroprotection and, potentially, a window of opportunity to utilize these mechanisms in the clinic to treat patients with stroke and other CNS disorders.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Brain / blood supply
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Ischemia / physiopathology*
  • Brain Ischemia / prevention & control
  • Disease Models, Animal
  • Erythropoietin / metabolism
  • Humans
  • Ischemic Preconditioning
  • Neuroprotective Agents / therapeutic use


  • Neuroprotective Agents
  • Erythropoietin