Understanding the molecular mechanisms of spinal cord cavitation after spinal cord injury

Surey, Sarina (2015). Understanding the molecular mechanisms of spinal cord cavitation after spinal cord injury. University of Birmingham. Ph.D.

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Abstract

Spinal cord injury (SCI) is a neurodegenerative disease with research centered on axon regeneration and preservation to cure paralysis. Mice and rats are widely studied and experienced models used to imitate SCI due to differences in vascular disruption, blood vessel loss and cavitation at SCI epicenters. This study investigates sub-acute SCI responses, documenting angiogenic/inflammatory factors and matrix deposition in both species. Although cavitation was absent in mice, the lesion site in rats was larger at 8 and 15 days post lesion (dpl). Absence of cavitation in mice correlated with increased levels of pro-angiogenic/wound healing factors within the wound compared to rats at 8 dpl, coinciding with microarray analysis along with increased axonal sparing at T7 and T9 spinal segments. Despite similar deficits in thermal sensitivity 2 hours after injury, by 7 days the responses were comparable to controls in both species. Furthermore, inducing inflammation directly after injury using zymosan resulted in inflammatory-induced angiogenic responses between both species at 8 dpl, contributing to tissue damage and micro-cavities in the CNS. In conclusion angiogenic responses in mice attenuates wound cavitation, reducing secondary axon damage and thus induces axon sprouting/regeneration. These results suggest potential therapeutic utility of manipulating angiogenic/inflammatory responses after human SCI.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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