Novel method to study autonomic nervous system function and effects of transplantation of precursor cells on recovery following spinal cord contusion injury

by 1973- Nout, Yvette Stephanie

Disruption of bladder and sexual function are major complications following spinal cord injury (SCI). To investigate these behaviors in a rat model of SCI, we developed a method to monitor micturition and erectile events by telemetry. Pressure monitoring has been described for recording penile erections in awake rats and involves placement of a catheter into the corpus cavernosum of the penis. We developed a variation on this technique involving pressure monitoring within the bulb of the corpus spongiosum penis (CSP). Using this technique we can record both erectile and micturition events. This technique was validated in 10 male rats and we demonstrated that telemetric recording of CSP pressure provides a quantitative and qualitative assessment of both penile erections and micturitions. Subsequently we monitored CSP pressures in 7 male rats subjected to SCI. We demonstrated that monitoring of CSP pressure in conscious rats is a valuable and reliable method for assessing recovery of autonomic function. Although recovery of micturition occurs in rats following incomplete SCI, recovery is limited and voiding remains inefficient. Moreover, changes consistent with spasticity and/or hyperreflexia were determined through waveform analysis. ii To repair the injured spinal cord cell transplant strategies are being developed since they appear to reduce secondary damage and promote regeneration. We examined the effect of transplanting glial restricted precursor (GRP) cells and elevating cyclic adenosine monophosphate (cAMP) concentrations on recovery of autonomic functions following SCI in 53 rats. When compared to an operated control group no beneficial effects of this cell transplantation technique were found with regards to behavioral outcomes. Histopathological analysis showed survival, migration, and differentiation of GRP cells within the spinal cord. Transplanted GRP cells were well integrated in the spared host tissue and animals that had received GRP cells had more tissue throughout the lesion region and at the lesion center. Although elevation of cAMP appeared to reduce the area of spinal cord occupied by graft tissue, cAMP favored differentiation of GRP cells into oligodendrocytes. The transplantation technique used here did not affect serotonergic input to the neurons in the lumbosacral spinal cord that regulate micturition and sexual behavior. iii This thesis is dedicated to my parents Robert and Frances Nout who taught me the value of education and perseverance. “Carpe Diem” iv