REGENERATION OF ADULT AXONS IN WHITE-MATTER TRACTS OF THE CENTRAL-NERVOUS-SYSTEM

It is widely accepted that the adult mammalian central nervous system (CNS) is unable to regenerate axons(1), In addition to physical or mol ecular barriers presented by glial scarring at the lesion site(2-4), i t has been suggested that the normal myelinated CNS environment contai ns potent growth inhibitors(5,6) or lacks growth-promoting molecules(1 ,7). Here we investigate whether adult CNS white matter can support lo ng-distance regeneration of adult axons in the absence of glial scarri ng, by using a microtransplantation technique(8) that minimizes scarri ng(9) to inject minute volumes of dissociated adult rat dorsal root ga nglia directly into adult rat CNS pathways. This atraumatic injection procedure allowed considerable numbers of regenerating adult axons imm ediate access to the host glial terrain, where we found that they rapi dly extended for long distances in white matter, eventually invading g rey matter. Abortive regeneration correlated precisely with increased levels of proteoglycans within the extracellular matrix at the transpl ant interface, whereas successfully regenerating transplants were asso ciated with minimal upregulation of these molecules, Our results demon strate, to our knowledge for the first time, that reactive glial extra cellular matrix at the lesion site is directly associated with failure of axon regrowth in vivo, and that adult myelinated white matter trac ts beyond the glial scar can be highly permissive for regeneration.