RNA synthesis in pons necessary for maintenance of bladder overactivity after cerebral infarction in rat.

Abstract

PURPOSE The maintenance of long lasting bladder overactivity caused by cerebral infarction is believed to require transcription in the pontine micturition center. Therefore, we examined the influence of the RNA synthesis inhibitor actinomycin D (Banyu Pharmaceutical Co., Ltd., Tokyo, Japan) on bladder overactivity induced by left middle cerebral artery occlusion. MATERIALS AND METHODS Rats under halothane anesthesia were injected with actinomycin D or vehicle (mannitol) into the bilateral dorsal pontine tegmentum, followed by middle cerebral artery occlusion. Awake rats were cystometrically examined for 12 hours. The expression of c-fos and zif268 mRNA in the dorsal pontine tegmentum was monitored with real-time polymerase chain reaction. RESULTS Injection of actinomycin D produced a significant decrease in bladder capacity in sham operated rats but bladder capacity returned to control levels before sham operation within 6 hours. In cerebral infarcted rats pretreated with vehicle bladder capacity was significantly decreased after middle cerebral artery occlusion and it remained consistently below half of pre-occlusion capacity. Actinomycin D blocked the decrease in bladder capacity in cerebral infarcted rats. In actinomycin D treated cerebral infarcted rats bladder capacity gradually recovered and returned to the control level before middle cerebral artery occlusion within 10 hours. Actinomycin D suppressed an increase in c-fos mRNA expression 1 hour after middle cerebral artery occlusion as well as in zif268 3 hours after occlusion. Administering actinomycin D 0.5 or 1 hour after middle cerebral artery occlusion also suppressed bladder overactivity until at least 10 hours after occlusion but injection 3 hours after occlusion did not. CONCLUSIONS These results indicate that an RNA synthesis inhibitor can prevent a late stage of bladder overactivity. Transcription in the dorsal pontine tegmentum was found to be necessary to maintain the long lasting bladder overactivity caused by cerebral infarction.

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@article{Yokoyama2003RNASI, title={RNA synthesis in pons necessary for maintenance of bladder overactivity after cerebral infarction in rat.}, author={Osamu Yokoyama and Satoshi Yotsuyanagi and Hironobu Akino and Horihiro Moriyama and Yosuke Matsuta and Mikio Namiki}, journal={The Journal of urology}, year={2003}, volume={169 5}, pages={1878-84} }