Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats.
OBJECTIVE
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-[14C] acetyl-coenzyme A to [14C] 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 CI 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.
Nakai
M
M
Department of Urology, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui, Japan. shoujimonaka@yahoo.co.jp
Akino
H
H
Kaneda
T
T
Matsuta
Y
Y
Shiyama
R
R
Tanase
K
K
Ito
H
H
Aoki
Y
Y
Oyama
N
N
Miwa
Y
Y
Yokoyama
O
O
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005260:Female; D007189:Indans / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D002795:Choline O-Acetyltransferase