Ibrahim, A; (2012) The use of olfactory ensheathing cells to promote regeneration of axons of central nervous system neurons. Doctoral thesis , UCL (University College London).

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Abstract

The mammalian central nervous system (CNS), including that of humans, has a poor capacity to repair and regenerate after injury. The outcome of brain and spinal cord injuries is a devastating loss of function and profound disability to the patient and tremendous socio‐economic burden to society. In this thesis, I first developed a behavioural model of brachial plexus dorsal root avulsion injury quantifying the subsequent behavioural deficit. Secondly, I transplanted olfactory bulb ensheathing cells in the dorsal root lesions and carried out functional, anatomical, electrophysiological assessments. The data showed that while dorsal roots avulsion injury of C6 to T1 created a permanent climbing deficit, the lesioning of 3 or fewer roots produced a less severe form of the deficit and rats were still able to climb by masking the effects of the lesion with time. After transplanting OECs into the dorsal root lesions, 70% of rats had restoration of paw grasping function, starting from 2‐3 weeks post surgery while none of rats without OEC transplant recovered climbing function. The transplanted cells induced a mass of reactive tissue which served as a bridge for regenerating axons to cross over into the spinal cord. Individual axonal fibres were detected (labelled with anterograde axonal tracer) crossing the dorsal root entry zone, entering the spinal cord, arborising within the laminae of the spinal cord grey matter. 6‐8 weeks after receiving OEC transplants, 7 out of 8 rats had cord dorsum field potentials detected at the cord after stimulating the median nerve. In the control group of 4 rats with chronic lesions but without OECs transplant, none showed cord dorsum potential nor cuneate responses up to 8 weeks after surgical intervention. I concluded that OEC transplants promote recovery of paw grasping functions and electrophysiological transmission in a dorsal root injury model.

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