Neurogenically mediated cystitis in rats: An animal model

Purpose: Pseudorabies virus (PRV) is a useful tool for mapping the control circuitry of the spinal cord. In the process of mapping CNS regulatory pathways far the lower urinary tract, a hemorrhagic change in the bladder was observed that was not overtly evident in other pelvic organs. The relationship between the appearance of hemorrhagic changes in the bladder and the evolution of PRV induced changes in the spinal cord was therefore explored. Materials and Methods: Sprague-Dawley rats were injected with PRV into the ACD tail-muscle. Bladder and CNS fixation were achieved by transcardial perfusion with formaldehyde. Multi-level sections were obtained from T8 through S4. Fixed tissue was stained and evaluated by light microscopy. Immunohistochemical stains were carried out for PRV and NOS on spinal cord tissue. We were therefore able to evaluate the relationship between the manifestation of the hemorrhagic cystitis, appearance of the PRV in the spinal cord and evidence of CNS inflammation. Results: The evolution of hemorrhagic cystitis paralleled the evidence of inflammation in the thoraco-lumbar and sacral cord. These bladders contained 5 to 9 mi. of bloody urine (a normal rat bladder contains 1 to 2 mi.). On cystomanometry (CMG) the bladders were acontractile. No PRV could be cultured in the hemorrhagic bladders. The histological changes observed in the bladder represent true inflammation. Conclusion: There was no obvious explanation for these changes other than the associated inflammatory changes in the spinal cord. The findings are consistent with the hypothesis that a spinal cord stress, via an unknown metabolic pathway, can result in dramatic, neurogenically mediated changes in the bladder.