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UBC Theses and Dissertations

Peripheral plasticity after spinal cord injury and ramifications for cardiovascular function Ramer, Leanne Margaret


Cardiovascular problems create life-long challenges for people living with spinal cord injury (SCI). When SCI occurs above the sixth thoracic segment (T6), it isolates spinal circuitry governing the critical splanchnic vascular bed, and creates the conditions for autonomic dysreflexia (AD), episodic hypertension instigated by sensory stimulation below the level of SCI. Most experiments investigating mechanisms of AD describe plasticity in the injured spinal cord. In this dissertation, I examined injury-induced changes at two peripheral loci critical to AD, the dorsal root ganglion (DRG) and mesenteric arteries. I used adult Wistar rats and performed complete transection SCI at T3 or T10: while both injuries produce hind limb paralysis, only the former is accompanied by AD. In the DRG, I found that T3 SCI triggered somatic hypertrophy in a specific subset of nociceptors, those expressing the capsaicin receptor (TRPV1). SCI-induced hypertrophy occurred in DRGs caudal to SCI and was most pronounced in lumbosacral ganglia. Intriguingly, SCI-induced hypertrophy was much more pronounced after T3 than T10 SCI. Importantly, when I used capsaicin to selectively eliminate TRPV1-positive projections to the lumbosacral spinal cord, the severity of AD was dramatically reduced. Next I examined glial, immune and vascular constituents of the lumbar DRG following SCI. I found that T3, but not T10 SCI activated satellite cells and macrophages in the DRG, and provoked mast cell accumulation in the adjacent spinal nerve. SCI at both levels promoted angiogenesis in the DRG and ingrowth of sympathetic ganglionic axons. In the superior mesenteric artery (SMA), I used in vitro myography to examine the role of cyclooxygenase (COX) enzymes in phenylephrine (PE) hyper-responsiveness after T3 SCI. I found that PE hypersensitivity was reversed by specific inhibitors of COX-2 and that COX-2 was upregulated in the SMA after T3 SCI. In an additional set of experiments, I found that recurrent episodes of AD, induced intentionally during recovery from SCI, exacerbated PE hyper-responsiveness in the SMA. These findings identify SCI-induced changes in the periphery that may contribute to AD by augmenting sensory input to the spinal cord or sympathetically-mediated vasoconstriction. These SCI-provoked effects may represent new therapeutic targets to treat AD.

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