Spontaneous regeneration of cut axons in adult rat brain

Abstract

Lesions with precisely defined boundaries were made, in adult rat brains, with a new type of cutting device that remained implanted during various survival times. The subsequent events were followed histologically in silver-stained (including Fink-Heimer) horizontal sections, with myelin and nuclear counterstains. The devices, inserted vertically through the dorsal surface of the brain until they met the floor of the skull, consisted of a horizontal cutting wire (0.9--2.6 mm long) between two vertical support wires, all 90 micrometers diameter. Following fixation of the brain, the device was removed from its ventral surface; thus, the channels left by the support wires appeared as two holes in horizontal sections, clearly marking the limits of the cut. The extents of the tissue cut by, and that passively deflected around, such devices were characterized from mearsurements of brains examined immediately after an incision was made and from degeneration studies after 3-day implantations. After implantations of 18--230 days, the severed axons no longer abutted the line of such lesions, as seen initially; now axons were often observed to extend alongside the lesion, then to bend and course around the support wire. Such "detours' ' curved back into the injured tracts, seeming to reconnect them appropriately. Detours had begun by 3--8 days, and end-swellings were frequently seen on their reoriented axons. Neither collateral sprouting of spared axons nor passive deformation of brain tissue was consistent with the findings. It is concluded that a massive and reconstructive regeneration of cut axons occurred around the ends of lesions made by the cutting devices.

Neuritic Outgrowth Associated with Astroglial Phenotypic Changes Induced by Antisense Glial Fibrillary Acidic Protein (GFAP) mRNA in Injured Neuron–Astrocyte Cocultures

“…The impact of microglia-derived factors on the CNS lesion (Giulian et al, 1994) and the inhibitory role of oligodendrocytes on axon growth (Schnell and Schwab, 1990;Lang et al, 1995) have been well documented. A second limitation is that this model does not include the three dimensions of a tissue and thus limits intercellular contacts and excludes, for instance, the possibility for axons to regenerate around a lesion (Foerster, 1982). Altogether, this model must be considered at face value, i.e., as a basis to study specifically the consequences of astrocytic reactivity on axonal growth.…”

Evidence that endogenous beta nerve growth factor is responsible for the collateral sprouting, but not the regeneration, of nociceptive axons in adult rats.

“…Whereas collateral sprouting, both during development and later, is a characteristic of normal undamaged nerves, and is essentially confined to target tissues (12,13), elongation is seen in adults particularly in the form of regeneration of an axon after peripheral nerve damage. In adult mammals, large myelinated mechanosensory axons readily regenerate after they are crushed, but unlike both myelinated (14) and unmyelinated (15) nociceptive axons, they fail to sprout collaterals into denervated skin when they are intact (16); in contrast, within the adult mammalian central nervous system (CNS) collateral sprouting of undamaged axons is the more readily evoked behavior (17), and axonal regeneration either fails to occur or occurs only under special conditions (18,19). Of particular interest, regenerating axons are almost uniformly successful when in competition with collaterally sprouting axons for occupancy of common target tissues (reviewed in ref.…”

Circadian Locomotor Rhythms, but Not Photoperiodic Responses, Survive Surgical Isolation of the SCN in Hamsters

“…Some elements of the adult central nervous system display neural plasticity in response to injury (Foerster, 1982;Phelps and Saporta, 1988;Reier and Houle, 1988;Reier et al, 1989). NPY fibers from host SCN-lesioned animals reach SCN grafts (Lehman et al, 1987;Silver et al, 1990).…”