Effects of nicotine on blood flow and delayed neuronal death following intermittent transient ischemia in rat hippocampus
Effects of nicotine on blood flow and delayed neuronal death following intermittent transient ischemia in rat hippocampus
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DOI：
10.2170/jjphysiol.50.585
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发表时间：
2000-12-01
期刊：
影响因子：
--
通讯作者：
Sato, A
中科院分区：
文献类型：
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作者：
Kagitani, F;Uchida, S;Sato, A
最近通过激活源自 Meynert 基底核和基底前脑间隔复合体的胆碱能神经元并投射到皮质和海马，从而激活烟碱乙酰胆碱受体（nAChR），从而证明了大脑皮层和海马中的胆碱能神经血管舒张反应，与代谢性血管舒张无关（参见 Sate A 和 Sate Y 的评论：Neurosci） Res 14：242-274，1992；Sato A 和 Sate Y：Alzheimer Dis Assoc Disord 9：28-38，1995）。在本研究中，我们旨在检查 I.V. 刺激 nAChR 后海马区域血流量 (Hpc-BF) 是否会增加。注射尼古丁可以改善大鼠短暂性缺血后海马神经元的延迟死亡。使用激光多普勒流量计测量Hpc-BF。除永久结扎双侧椎动脉外，间歇性（每2分钟）短暂闭塞双侧颈动脉共6分钟，Hpc-BF下降至闭塞前水平的约16%，闭塞后5或7天，约70%的CA1海马神经元发生迟发性神经元死亡。通过注射尼古丁（30-100 微克/千克，静脉注射），Hpc-BF 呈剂量依赖性增加，与平均动脉压无关。闭塞前 5 分钟给予尼古丁 (30-100 杯/公斤)，轻微但显着减弱闭塞引起的 Hpc-BF 降低。短暂闭塞后发生的 CA1 海马神经元延迟死亡通过尼古丁（30-100 微克/千克）预处理减弱至总神经元的约 50%。结果表明，nAChR 刺激诱导的 Hpc-BF 增加可以防止缺血诱导的海马神经元延迟死亡。
A cholinergic neural vasodilative response in the cerebral cortex and hippocampus, independent of metabolic vasodilation, was recently demonstrated by activating the nicotinic acetylcholine receptors (nAChRs) via activation of cholinergic neurons originating in the nucleus basalis of Meynert and septal complex in the basal forebrain and projecting to the cortex and hippocampus (see reviews by Sate A and Sate Y: Neurosci Res 14: 242-274, 1992; Sato A and Sate Y: Alzheimer Dis Assoc Disord 9: 28-38, 1995). In the present study, we aimed to examine whether an increase in regional blood flow in the hippocampus (Hpc-BF) following stimulation of the nAChRs by I.V. injection of nicotine could improve the delayed death of the hippocampal neurons following transient ischemia in rats. Hpc-BF was measured by using a laser Doppler flowmeter. During intermittent (every 2 min) transient occlusion for a total of 6 min of bilateral carotid arteries besides permanent ligation of bilateral vertebral arteries, Hpc-BF decreased to about 16% of the preocclusion level, and 5 or 7d later, after the occlusion, delayed neuronal death occurred in approximately 70% of the CA1 hippocampal neurons. Hpc-BF was increased dose-dependently by injection of nicotine (30-100 mug/kg, I.V.), independent of mean arterial pressure. Nicotine (30-100 mug/kg) administered 5 min before occlusion slightly but significantly attenuated the occlusion-induced decrease in Hpc-BF. The delayed death of the CA1 hippocampal neurons occurring after transient occlusion was attenuated by pretreatment with nicotine (30-100 mug/kg) to approximately 50% of the total neurons. The results indicate that nAChR stimulation-induced increases in Hpc-BF can protect against ischemia-induced delayed death of hippocampal neurons.