'Ischemic tolerance' phenomenon found in the brain

Kazuo Kitagawa, Masayasu Matsumoto, Masafumi Tagaya, Ryuji Hata, Hirokazu Ueda, Michio Niinobe, Nobuo Handa, Ryuzo Fukunaga, Kazufumi Kimura, Katsuhiko Mikoshiba, Takenobu Kamada

Research output: Contribution to journalArticlepeer-review

432 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)21-24
Number of pages4
JournalBrain Research
Issue number1
Publication statusPublished - 24-09-1990
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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