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Title: The effects of inflammation on the regeneration and degeneration of axons in the CNS
Author: Acosta-Saltos, F. C.
ISNI:       0000 0004 5366 2833
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Microglia have neurotoxic and neuroprotective effects. The aim of the current project was to investigate the effects of perineuronal microglial activation on axonal regeneration in adult rats and the effects of prolonged neuroinflammation on foetal mouse brain. In contrast to the PNS, the CNS only displays limited axonal regeneration after injury and little perineuronal inflammation. Inflammation around the cell bodies of axotomised neurons has been demonstrated to promote CNS regeneration. Polyinosinic:polycytidylic acid (Poly I:C) is an inflammatory agent. Following delivery of Poly I:C into the motor cortex and a concomitant C4 dorsal corticospinal tract (CST) injury, rats exhibited more CST axons in the cervical spinal cord and less retraction from the injury site than controls. Following facial nerve axotomy, Poly I:C injections adjacent to the facial nucleus accelerated functional recovery. Viral vectors carrying Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) were injected into motor cortex. GM-CSF virus reduced retraction of corticospinal axons from a spinal cord injury site. Behavioural studies of forelimb movements showed that C4 injury had a greater impact on fine distal movements, particularly reaching and grasping, which are known to be controlled by the CST. Treating rats with GM-CSF virus showed a trend towards improved forelimb sub-movements and significantly aided the reaching function recovery. Perinatal activation of periventricular phagocytes has been suggested to result in white matter damage, causing persistent motor disabilities. Transuterine injections of control or GM-CSF virus targeting the lateral ventricles of mice at gestational day 14, resulted in a widespread virally-transduced cells. Greater numbers of phagocytic and activated microglia were present in the areas of viral transduction. There was increased inflammation in the periventricular white matter. Although, the level of transduction remained relatively constant with increasing time, inflammation decreased, suggesting that GM-CSF toxicity is high before or around birth.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available