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‘Ischemic tolerance’ phenomenon found in the brain

Brain Research
Publication Date
DOI: 10.1016/0006-8993(90)90189-i
  • Gerbil
  • Cerebral Ischemia
  • Ischemic Tolerance
  • Hippocampus
  • Delayed Neuronal Death
  • Microtubule Associated Protein 2
  • Biology
  • Medicine


Abstract We investigated the possibility that neuronal cells given a mild ischemic treatment sufficient to perturb the cellular metabolism acquired tolerance to a subsequent, and what would be lethal, ischemic stress in vivo. Cerebral ischemia was produced in the gerbils by occlusion of both common carotids for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. Minor 2-min ischemia in this model depletes high-energy phosphate compounds and perturbs the protein synthesis, but nerver causes neuronal necrosis, and therefore was chosen as mild ischemic treatment. Single 2-min ischemia 1 day or 2 days before 5 min ischemia exhibited only partial protective effects against delayed neuronal death. However, two 2-min ischemic treatments at 1 day intervals 2 days before 5 min ischemia exhibited drastically complete protection against neuronal death. The duration and intervals of ischemic treatment, enough to perturb cellular metabolism and cause protein syhthesis, were needed respectively, because neither 1-min ischemia nor 2-min ischemia received twice at short intervals exhibited protective effects. This ‘ischemic tolerance’ phenomenon induced by ischemic stress — which is unquestionably important — and frequent stress in clinical medicine, is intriguing and may open a new approach to investigate the pathophysiology of ischemic neuronal damage.

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