Oxidative stress and neurodegeneration in the ischemic overactive bladder.
OBJECTIVE
The central and peripheral nervous systems are highly sensitive to ischemia and oxidative stress. We searched for markers of oxidative injury and examined neural density in the rabbit ischemic overactive bladder.


METHODS
Blood flow and oxygenation were recorded during cystometrogram in overactive and control rabbit bladders at weeks 8 and 16 after the induction of ischemia. Oxidative products and neural density were assessed by enzyme immunoassay and immunohistochemical staining, respectively. Reverse transcriptase-polymerase chain reaction was done to determine the gene expression of nerve growth factor and its receptor p75. The effect of acute oxidative stress was examined in tissue culture medium containing H(2)O(2).


RESULTS
Overactivity produced repeating cycles of ischemia/reperfusion and hypoxia/reoxygenation in the ischemic bladder, leading to oxidative and nitrosative products. Neural density in the 8-week ischemic bladder was similar to that in controls, while neurodegeneration was evident after 16 weeks of ischemia. Nerve growth factor gene levels initially increased at week 8 but significantly decreased at week 16 after the induction of ischemia. Gene levels of p75 decreased after 8 weeks and remained lower than in controls after 16 weeks of ischemia. Acute oxidative stress decreased nerve growth factor protein release in culture medium. The antioxidant enzyme catalase had no significant effect on control tissues but it partially protected nerve growth factor from H(2)O(2) injury.


CONCLUSIONS
Ischemia may have a role in bladder neuropathy. Overactivity under ischemic conditions produces noxious oxidative products in the bladder. Neurodegeneration in bladder ischemia may involve a lack of nutrients, hypoxia and overactivity induced free radicals. Nerve growth factor and its receptors may regulate neural reactions to oxidative injury.
Azadzoi
Kazem M
KM
Department of Urology, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA. kazadzoi@bu.edu
Yalla
Subbarao V
SV
Siroky
Mike B
MB
D000818:Animals; D002374:Catalase / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D007511:Ischemia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D020932:Nerve Growth Factor / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D011817:Rabbits; D020800:Receptor, Nerve Growth Factor / Q000235:genetics; D001743:Urinary Bladder / Q000098:blood supply* / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D002374:Catalase