Kalsi, Pratipal Singh; (2021) Olfactory ensheathing cells for central nervous system repair: A ventral root model for intraspinal brachial plexus repair in the rat. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Brachial plexus avulsion injuries occurring at the central nervous system and peripheral nervous system transition zone are often referred to as longitudinal spinal cord injuries. A number of surgical procedures, including intraspinal ventral root reimplantation, have been devised to treat these injuries but hand function rarely recovers and there is no cure. A number of preclinical and clinical studies have attempted to use cellular therapies for spinal cord injury repair. To this regard the olfactory ensheathing cell, obtained from the olfactory pathways, has shown promise but remains controversial. These cells have not previously been investigated in a brachial plexus repair model but their reparative and regenerative properties gives them investigative potential. In order to replicate a brachial plexus injury affecting the human hand, we have devised a rodent model of C8 ventral root repair. We used histological analysis and immunohistochemistry staining with neurofilament and glial fibrillary acidic protein to assess the repair. Tests were developed to assess neuronal continuity across the repair site using retrograde tracers. Functional tests were developed to quantify forepaw injury and recovery. Once a model was established, four experimental study groups consisting of left C8 ventral root avulsion, reimplantation, and transplantation of mucosal and bulb olfactory ensheathing cells were devised. Our results demonstrate that reimplantation of the ventral root after avulsion led to a significantly improved left paw spread recovery and survival of motor neurones compared to the avulsion group. Transplantation of mucosal and bulb olfactory ensheathing cells led to a significantly improved recovery in paw spread, increased survival of motor neurones, and less forepaw deformity and autotomy, compared to the reimplantation group. These results suggest that olfactory ensheathing cells can promote central nervous system recovery in adult rats and add promise to their translational potential for brachial plexus repair in humans.

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