Davies, Stephen John Alexander; (1996) Growth of axons in fibre tracts of the adult central nervous system. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

A number of experiments have implicated white matter tracts as the site for failure of regeneration in the adult mammalian central nervous system (CNS) (Cajal, 1928; Schwab, 1990). In order to assess the ability of adult white matter tracts to sustain and direct new axonal growth, I have used an air pressure pulse microtransplantation technique, to introduce minute volumes of suspensions of mouse embryonic neurons and glia directly into and completely enclosed within a number of different adult rat CNS tracts. Using mouse specific monoclonal markers (M6 and Thy1.2), I have observed rapid, long interfascicular axon growth from the transplants through the host white matter, aligned with tract glial and axonal elements and invading host terminal fields. These results show that adult white matter tracts are a highly permissive substrate for embryonic axonal growth. I have demonstrated that the interface between the embryonic neural microtransplants and the adult tract permits the ingrowth of adult tract axons. Injection of biotin dextran tracer into the adult fimbria of rat hosts, labelled host axons within the neuropil of hippocampal intratract microtransplants. Host innervation of the embryonic microtransplants was confirmed by transection of the host fimbrial axons, allowing electron microscopy of their degenerating synapses within the intrafimbrial grafts. To examine the ability of cut adult central nervous system axons to regenerate through an aligned but reactive adult tract glial pathway, I have designed a microlesion approach, in which a micropipette is used to cut a contingent of p75 immuno-positive adult cingulate axons. No glial scar or necrotic tissue cavity were formed at the lesion site and immunohistochemistry for GFAP (for astrocytes) and OX42 (for microglial) showed that the adult tract glial framework (Suzuki and Raisman, 1992) rapidly regained it's normal alignment. Specific upregulation of p75 immuno-reactivity in the proximal segments of the cut axons showed that regeneration of these axons through the lesion site was totally blocked, even in the absence of a glial scar.

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