期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 73, 期 4, 页码 901-910出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0091-3057(02)00939-5
关键词
nicotinamide; infarct volume; limit; dose response; time course; neurological deficit
资金
- NINDS NIH HHS [NS38653, NS14543, NS25372, NS36147] Funding Source: Medline
Background and purpose: Nicotinamide protects against brain damage in ischemia-reperfusion. However, the dosage and time of treatment require clarification. It is also not clear if nicotinamide can protect against both necrosis and apoptosis. Methods: Dose-response and time-effect studies were designed. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min. Different doses of nicotinamide were injected upon reperfusion. In time-effect studies, 500 mg/kg nicotinamide was administered at different times after the onset of reperfusion, Neurological finding scores were recorded. Infarct Volumes were measured. Results: In contrast to controls, neurological deficit scores and infarct volumes were greatly reduced by treatment with nicotinamide. The ED50 of nicotinamide was 239 +/- 79 mg/kg (P=.95). It was found that nicotinamide injected during the first 6 h of reperfusion could effectively inhibit the development of brain damage. The optimal dose of nicotinamide was 500 mg/kg and gave a maximal response. Conclusions: Poly(ADPribose) polymerase (PARP) plays a key role in DNA repair in stroke. Excessive PARP activity consumes NAD leading to energy depletion and neuronal damage. As an inhibitor of PARP, nicotinamide promotes the supply of energy. The results suggest that early application of nicotinamide at a suitable dosage significantly ameliorates necrotic and apoptotic brain injury, after focal ischemia-reperfusion. (C) 2002 Elsevier Science Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据