title: 'Ischemic tolerance' phenomenon found in the brain.
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 never 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 synthesis, 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.
authors: First Department of Internal Medicine, School of Medicine, Osaka University, Japan.
authors: K
authors: K
authors: Kitagawa
authors: M
authors: M
authors: Matsumoto
authors: M
authors: M
authors: Tagaya
authors: R
authors: R
authors: Hata
authors: H
authors: H
authors: Ueda
authors: M
authors: M
authors: Niinobe
authors: N
authors: N
authors: Handa
authors: R
authors: R
authors: Fukunaga
authors: K
authors: K
authors: Kimura
authors: K
authors: K
authors: Mikoshiba
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002470:Cell Survival; D005260:Female; D006624:Hippocampus / Q000473:pathology; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology; D013997:Time Factors