Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats
Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats
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DOI：
10.1016/j.neuroscience.2006.06.012
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发表时间：
2006-10-13
期刊：
影响因子：
3.3
通讯作者：
Yokoyama, O.
中科院分区：
文献类型：
--
作者：
Nakai, M.;Akino, H.;Yokoyama, O.
目的：研究脑缺血后额叶皮质胆碱能通路对排尿的功能贡献。此外，它被检查是否重新激活这一监管系统，使用乙酰胆碱酯酶抑制剂可以改善逼尿肌overactivity.Methods：左侧大脑中动脉闭塞（MCAO）在雌性Sprague-Dawley大鼠。测定脑缺血后胆碱乙酰转移酶（ChAT）的活性，以评价脑缺血后胆碱能神经元的损伤程度。通过测量1-[C-14]乙酰辅酶A转化为[C-14]乙酰胆碱，计算双侧皮质、海马和脑桥中的ChAT活性。在清醒假手术（SO）和脑梗死（CI）大鼠中研究了静脉或静脉注射中枢作用乙酰胆碱酯酶抑制剂盐酸多奈哌齐（DON）对膀胱测压的影响。要调查是否DON在前脑的影响，我们去脑大鼠后，Cl或SO，并调查cystometrography的影响静脉DON。结果：膀胱容量显着下降后MCAO，并保持低于一半的预闭塞能力。在静脉注射1.2 × 10（-2）nM/kg DON时，膀胱容量增加最大，变化率为52.8%（P < 0.05）。在静脉注射DON的病例中，膀胱容量增加最大的剂量为6 × 10（-2）pmol，变化率为95.8%（P < 0.01）。MCAO后24 h左侧皮质和海马ChAT活性降低（P < 0.05）。在去脑大鼠，低剂量的DON没有改变排尿parameters.Conclusions：这些结果表明，通过上调前脑毒蕈碱抑制机制，乙酰胆碱酯酶抑制剂改善逼尿肌过度活动脑梗死。(c)2006由Elsevier Ltd代表IBRO出版。
Purpose: The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity.Methods: Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[C-14] acetyl-coenzyme A to [C-14] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after Cl or SO, and investigated the effects on cystometrography of i.v. DON.Results: Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P < 0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P < 0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P < 0.05). In decerebrated rats, low dose of DON did not change micturition parameters.Conclusions: These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.