Guth_1981_J.Comp.Neurol_203_297

The failure of axonal regeneration in the transected spinal cord of mammals has been attributed to many factors, including an intrinsic lack of regenerative capacity of mature CNS neurons, mechanical obstruction of axonal elongation by glial-connective tissue scars, necrosis of spinal tissue resulting in cavitation, lack of trophic influences sufficient to sustain outgrowth, and contact inhibition resulting from the formation of aberrant synapses. Assessment of te relative importance of each of these factors requires animal models in which one or more of these pathological processes can be eliminated. We therefore examined the effects of spinal transection in the hibernating animal because, during hibernation, collagen formation is depressed while nerve regeneration and slow axonal transport are maintained. Midthoracic spinal transections were performed in hibernating ground squirrels and the spinal cords were examined histologically 1-6 months later. The lesion site was composed primarily of a loose accumulation of macrophages and showed minimal glial and collagenous scarring, or cavitation. There was extensive regeneration of intrinsic spinal cord and dorsal root fibers. These axons grew to the margin of the lesion where they turned abruptly and continued growing along the interface between the lesion and the spinal cord. We conclude (1) that mammalian spinal-cord neurons have considerable regenerative potential; (2) that such mechanical impediments as collagenous and glial scarring, cyst formation, and cavitation cannot provide the sole explanation of why regeneration in the mammalian CNS is abortive; and (3) that specific physical and chemical properties of the cells in the environment of the growth cone regulate the extent and orientation of regenerative axonal outgrowth.