Vigorous orientated fibre outgrowth of adult sensory axons after microtransplantation into the central nervous system grey matter : an investigation into orientation and possible growth substrates
The mature mammalian central nervous system (CNS) is unable to regenerate successfully after injury. This regeneration failure is in contrast to the peripheral nervous system (PNS) which can regenerate. Innumerable investigations have attempted to discover the underlying reasons for this behaviour and especially over the last two decades, the general understanding of many of the diverse contributing factors has valuably increased.In the late 1980’s, CNS myelin was discovered to be the most important inhibitor of axonal outgrowth, a discovery which lead to profound research on the issue and resulted in the identification of several myelin inhibitory proteins and a common corresponding receptor. However, since the late 1990’s, strong evidence has arisen, which supports the notion that the inhibitory molecules of the glial scar might play a greater role in preventing regeneration after CNS injury. In this context, two transplantation studies conducted by Silver and colleagues seemed ground-breaking: with the help of a special microtransplantation technique, which induces only minimal tissue damage at the lesion site, adult sensory neurons were transplanted into the adult CNS white matter and demonstrated vigorous axon regeneration which extended along unperturbed mature myelin pathways as well as along Wallerian degenerating fibre pathways. Host astrocytes and their processes were deemed to be the substrate responsible for supporting such strongly orientated regeneration along white matter tracts. These important investigations were restricted to adult rat white matter, with no correlative investigations in adult grey matter being performed. Therefore, in the present investigation, adult sensory neurons were microtransplanted into both mature CNS white and grey matter. The experiments revealed that the adult CNS grey matter can, as well as the adult CNS white matter, be a highly permissive environment for robust axonal outgrowth from the donor adult neuronal population. Interestingly, the regenerating PNS axons did not follow the random pattern of host astroglia and their processes, but demonstrated substantially orientated outgrowth, possibly directed towards certain thalamic nuclei. In an attempt to clarify the issue of the substrate responsible for supporting such strong axonal outgrowth, double immunofluorescence could only demonstrate occasional co-localisation of donor axons with host blood vessel walls, astrocytes, microglia and CNS myelin. Donor axons did, however, seem to employ the cell-adhesion molecule (CAM) L1 for interactions with host neuronal processes.
info:eu-repo/classification/ddc/610, Medizin, Zentralnervensystem, Regeneration, Transplantation, Central Nervous System, Dorsal Root Ganglia
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