Patients with chronic traumatic encephalopathy (CTE) show loss of central white matter, central gray matter, and cortical gray matter with increasing post-traumatic survival. The majority of experimental studies using animals have, however, discussed only the ultrastructural pathophysiology of injured central white matter leading to secondary axotomy and the formation of axonal terminal bulbs. Using the stretch-injured optic nerve model in adult guinea pigs, the present study provides novel quantitative data concerning Wallerian degeneration of disconnected axonal fragments following secondary axotomy out to 12 weeks after injury to an optic nerve. The time course of Wallerian degeneration at the level of an individual nerve fiber is comparable to that reported in earlier studies over 48 h to two weeks after secondary axotomy. But only a relatively small proportion of nerve fibers within the optic tract degenerate via Wallerian degeneration during the first two weeks. Rather, examples of each of the three stages of Wallerian degeneration-acute axonal degeneration, latency of the distal axonal segment, and granular fragmentation-occur within the optic tract across the entire experimental survival of 12 weeks used in the present study. This data suggests that some nerve fibers initiate Wallerian degeneration days and weeks after the initial time of mechanical injury to an optic nerve. The number of intact nerve fibers continues to fall over at least three months after injury in the stretch-injury model of traumatic axonal injury. It is suggested that these novel findings relate to the mechanism(s) whereby central white matter volume decreases over months and years in CTE patients.
Keywords: Wallerian degeneration; central myelinated nerve fibers; secondary axotomy; stretch-injury.