An examination of the cellular and inflammatory response in rats after spinal cord injury ; the effects of age and survival time

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Spinal cord injury (SCI) is a complex and devastating condition that has a life-long effect on patients’ quality of life, their family, carers and society. Currently there is no cure for SCI, and no proven treatment in the acute phases of SCI. Tissue loss and varying degrees of functional impairment result from a SCI, and only limited repair is exhibited. A great deal of research has focused on reducing the degenerative effects that occur during the secondary injury phase of injury to order to promote tissue repair and regeneration. The immune and inflammatory response is thought to play a significant role in this process, albeit with both beneficial and detrimental responses reported. Most research to date has concentrated on adult SCI, yet it has been suggested that the young show better functional recovery compared to adults both for humans and in a variety of animal models. The current research project used an animal model of contusive SCI to compare adult (9wk), juvenile (5wk) and infant (P7) Sprague-Dawley rats. One cohort (n=108) was assessed over a 6 week post-injury period for 1) locomotor function using established and newly developed scoring systems, 2) injury progression using histology, and 3) inflammatory cell changes using immunohistochemistry. A second cohort (n=97) was assessed acutely (1h, 24h and 1wk post-injury) for inflammatory mediators using flow cytometry on the injured tissue homogenate and multiplex cytokine ELISA on the tissue supernatant. Finally, an in vitro study was conducted to explore the possibility of modulating different macrophage populations using conditioned media to create a more anti-inflammatory microenvironment. The results described in this thesis show that following a SCI of comparative severity there were significant differences between adult and infant injury progression and presentation, inflammatory responses, and behavioural recovery. This research reinforced the inherent difficulties in modelling infant conditions for comparative studies, but it has also highlighted two important avenues of research to be pursued. 1) A better understanding of SCI progression in the young is needed to inform how paediatric SCI is treated and managed, and 2) targeted modulation of the inflammatory response in adult SCI patients may be a promising avenue for better functional recovery.
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