Induction of ischemic tolerance in rat cortical neurons by 3-nitropropionic acid: chemical preconditioning

被引:35
作者
Weih, M
Bergk, A
Isaev, NK
Ruscher, K
Megow, D
Riepe, M
Meisel, A
Victorov, IV
Dirnagi, U
机构
[1] Charite, Dept Neurol, Berlin, Germany
[2] Russian Acad Med Sci, Brain Res Inst, Moscow, Russia
[3] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany
关键词
cerebral ischemia; hypoxia; cell culture; transcription factors; stroke; oxidative phosphorylation;
D O I
10.1016/S0304-3940(99)00594-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Sublethal ischemia leads to increased tolerance against subsequent ischemia. We investigated whether tolerance could also be elicited by mild respiratory-chain inhibition (chemical hypoxia) in a rat neuronal-cell enriched culture system. 3-Nitropropionic acid (3-NPA) caused a concentration-dependent inhibition of succinate-dehydrogenase. Two hours preconditioning with 3-NPA 24-48 h before oxygen-glucose deprivation (OGD) reduced neuronal damage morphologically and reduced lactate deydrogenase (LDH) release up to 72% compared to sham-treated sister cultures without 3-NPA. In an attempt to elucidate transcriptional mechanisms, we found no rapid translocation of the hypoxia-sensitive transcription factors N F-KB or hypoxia-inducible factor-1 (HIF-1) at 3-NPA concentrations sufficient to trigger tolerance against OGD. In accordance to previous in vivo and brain slice data, we conclude that 8-NPA chemically induces tolerance against oxygen-glucose deprivation in vitro. However, the underlying mechanisms remain elusive. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:207 / 210
页数:4
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