ROLE OF ISCHEMIA AND OXIDATIVE STRESS IN BLADDER NEURODEGENERATION Kazem M' Azadzoi, Subbarao V' Yal

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ROLE OF ISCHEMIA AND OXIDATIVE STRESS IN BLADDER
NEURODEGENERATIONKazem M. Azadzoi, Subbarao V.
Yalla and Mike B. SirokyVA Boston Healthcare
System and Boston University School of Medicine

• AIMS Most cases of bladder overactivity are
  associated with neurodegeneration. Our goal was
  to search for markers of oxidative stress and
  neural injury in the ischemic bladder using an
  established rabbit model of pelvic ischemia.
• METHODS The methods involved
• Measuring bladder wall blood flow and PO2 at rest
  and after contraction.
• Enzyme immunoassay of oxidative products.
• Immunohistochemical staining of neural fibers.
• Image analysis of neural density.
• RT-PCR analysis of NGF and NGF-receptor
  expression.
• RESULTS
• TABLE 1
• 
  CONTROL BLADDER ISCHEMIC BLADDER
  
• 
  Blood flow pO2 Blood flow pO2
• Basal level 6.8 0.7 41.5
  6.2 3.3 0.4 26.7 4.2
• At peak contraction 4.6 0.5 37.3 5.4
  0.6 0.3 8.8 3.8 (I/H phase)
• End of contraction 8.1 0.6 46.4
  7.1 4.7 0.5 35 5.5 (RP/RO phase)
• Contraction- 3.0 1.8 / 10
  minutes 10.0 2.2 / 10 minutes
• frequency

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Effects of ischemia and oxidative stress on
bladder neural expression
Effects of ischemia and oxidative stress on NGF
expression
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• EFFECTS OF ISCHEMIA AND OXIDATIVE STRESS ON NGF
  GENE EXPRESSION
• Control 8 weeks 16 weeks
• NGF ?
• NGF-R ?
• GAPDH ?

EIA showed approximately three fold increase in
the levels of oxidatively modified product
isoprostane 8-epi PGF2 alpha in the ischemic
bladder in comparison to the controls.
CONCLUDING MESSAGE Our data suggest that the
mechanism of neurodegeneration in the overactive
bladder involves oxidative stress and neurotoxic
oxidative products.