Neurogenic bladder predisposes to recurrent urinary tract infections (UTI) and renal failure, and susceptibility is commonly ascribed to urinary stasis from elevated residual urine volumes. Escherichia coli UTI was modeled in the spinal cord-injured (SCI) rat with the hypothesis that SCI animals would require fewer bacteria to establish infection, have an exaggerated inflammatory response, and have delayed clearance of infection compared to normal-voiding controls. T10 SCI rats and controls had median infectious doses (ID50) of 102 and 105 CFU, respectively. Mean residual volumes in the SCI animals did not correlate with susceptibility to initiation of UTI or outcome. In the acute infection, control and SCI rats developed acute cystitis and pyelitis without acute differences in histopathological scores of inflammation. However, in vivo imaging of infected animals revealed persistently higher levels of bacteria in the SCI urine and bladders than were seen for controls over 2 weeks. Likewise, at 2 weeks, acute and chronic inflammatory infiltrates persisted in the bladders and kidneys of SCI rats, whereas inflammation largely resolved within the controls. Together these data demonstrate that SCI rats exhibit delayed clearance of infection and exaggerated inflammatory responses in bladders and kidneys; however, the severity of residual volumes does not predict increased susceptibility to UTI. These studies suggest that host-dependent mechanisms that are discrete from alterations in bladder physiology influence UTI susceptibility with the SCI-neurogenic bladder. This model will allow elucidation of SCI-neurogenic bladder-mediated changes in host response that yield UTI susceptibility and may lead to new preventative and therapeutic options.
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