Li, Ying; (1995) Axon growth in the adult rat spinal cord. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

The mouse species-specific marker, M6, showed that suspensions of embryonic mouse hippocampal neurons micro-injected into the cervical dorsal columns of immuno-suppressed adult rat spinal cord grew long, straight, and uniform axons rostrally and caudally for around 10 mm, with a clear preference for white matter. The donor axons dispersed among the host myelinated axons, parallel to them and to the aligned rows of interfascicular glial cell bodies. After circumscribed lesions in the cervical corticospinal tract, the course of astroglial activation was followed by GFAP immunostaining at survivals up to about 3 months. After a dense astrocytic scar had formed, labelling of the descending axons by anterograde transport from unilateral stereotaxic medullary micro-injections of anterograde tracers showed that substantial numbers of cut axons persisted, without retraction, in the central, macrophage-filled lesion area. The ends of the cut axons were expanded into a variety of shapes, with profuse local branches, and myelinated as far as their expanded tips by endogenous Schwann cells. A suspension of Schwann cells cultured from neonatal or adult rat sciatic nerve was micro-transplanted into the same positions as the lesions. In response to these exogenous Schwann cells, both ascending dorsal column axons and descending corticospinal axons sprouted much more rapidly and profusely than after lesions. Both cut and uncut axons gave rise to parallel branches which extended for considerable distances, and fasciculated with each other and with other tract axons. The Schwann cell grafts were also invaded by masses of fine, tortuous, varicose branches, similar to the terminal arborisations in the adjacent grey matter. Electron microscopy and P0 immunostaining showed that, from about 10 days after transplantation, the transplanted Schwann cells had myelinated a wide swathe of host axons. Preliminary experiments with micro-injection of populations of Schwann cells transfected in culture with gene constructs directing the over-expression of NGF and NT-3 modified the axonal sprouting responses. Preliminary functional tests showed recovery in a fine paw-reaching test.

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