Expression of neural plasticity related gene in the pontine tegmental areaof rats with overactive bladder after cerebral infarction

Purpose: We investigated the expression of the neural plasticity related ge nes c-fos, zif268, c-jun, brain-derived neurotrophic factor and tissue plas minogen activator in the pontine tegmental area in rats with overactive bla dder induced by cerebral infarction. Materials and Methods: Cerebral infarction was induced by left middle cereb ral artery occlusion in female Sprague-Dawley rats. Bladder activity was mo nitored by continuous infusion cystometrography in awake rats. Specimens we re obtained from the pontine tegmental area 1, 3, 5, 12 and 24 hours after cerebral infarction or sham operation. The effect of 0.1 mg./kg. intravenou sly of the N-methyl-D-aspartate glutamatergic receptor antagonist MK-801 on bladder activity, and c-fos and zif268 expression after middle cerebral ar tery occlusion were studied. Real-time reverse transcriptase-polymerase cha in reaction was performed with the LightCycler system (Roche Diagnostics, M annheim, Germany) to evaluate cerebral infarction influences on gene expres sion in the pontine tegmental area. Results: Bladder capacity in cerebral infarcted rats was significantly redu ced 1 to 24 hours after middle cerebral artery occlusion compared with that of sham operated rats (p < 0.05 to 0.01). One hour after occlusion mean c- fos messenger (m)RNA expression plus or minus standard error had significan tly increased to 18.9 +/- 4.0 in terms of its density relative to the outer control in a sample obtained immediately after occlusion compared with tha t in sham operated rats (p < 0.05). It returned to the control level within 3 hours after occlusion. Mean zif268 mRNA expression significantly increas ed to a relative density of 3.2 +/- 1.4 3 hours after middle cerebral arter y occlusion (p < 0.01) and returned to the control level within 5 hours aft er occlusion. The expressions of c-jun, brain-derived neurotrophic factor a nd tissue plasminogen activator was not influenced by occlusion. Pretreatme nt with MK-801 inhibited bladder overactivity and significantly reduced the expression of c-fos and zif268 mRNA in the Pontine tegmental area. Conclusions: These results indicate that the development of bladder overact ivity after middle cerebral artery occlusion is mediated by activation of a n N-methyl-D-aspartate receptor and accompanied by an increase in c-fos and zif268 mRNA expression in the pontine tegmental area.