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Pelvic neurovisceral plasticity following complete spinal cord injury

University of British Columbia

Spinal cord injury (SCI) interrupts communication between the brain and peripheral organs resulting in profound and long-lasting effects, including clinically important dysfunction of the pelvic viscera (PV). Sensory and autonomic peripheral neurons innervating the PV are contained in the dorsal root ganglia (DRG) and pelvic ganglia (PG), respectively. Previous studies have identified changes in these neurons after SCI, but questions remain about the relationship between injury level and changes in peripheral targets and ganglia. In this dissertation, I addressed these questions using male Wistar rats with a high thoracic transection (T3x), which eliminates the majority of supraspinal connections to sympathetic preganglionics (including those innervating the splanchnic bed and adrenal glands), or a high lumbar transection (L2x), which preserve these connections but directly damage neurons innervating the pelvic peripheral ganglia and PV. I examined gene expression changes in DRGs and PGs one month post-T3x using RNA sequencing and found indications for unexpected neuron-target interactions, including changes in growth factor signaling and cell communication. In the PG, decreased expression of tyrosine hydroxylase (TH) after T3x was supported by atrophy of sympathetic (TH-positive) neurons. SCI results in bladder hypertrophy, and though L2x resulted in increased bladder weights compared to both T3x and naïve animals, the expression of TH in the PG decreased and TH-positive neuron hypertrophy was only transient. These results indicate a more complex relationship between target size and neurotrophism than generally accepted. Examination of PV changes after high and low SCI revealed different patterns of bladder activity. Two days after injury, there was augmented bladder activity at low intravesical pressures in L2x compared to T3x and naïve animals. I found that disrupting signal transmission through the PG did not change the bladder activity patterns, however, bilateral adrenalectomy concurrent to L2x resulted in bladder activity patterns that more closely resembled the T3x injury. Further to this, circulating catecholamine levels were higher in animals with intact innervation to the adrenal gland, implicating adrenal function in bladder changes after SCI. The findings in this thesis highlight the importance of studying injury level both from the perspective of both local circuitry and systemic changes.

Text

2019-11-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/67915

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/