Fate of reactive axonal swellings induced by head injury

The fate of those reactive axonal swellings seen following head injury was assessed in cats subjected to mild to moderate fluid-percussion head injury. To allow for the ready visualization of any traumatically induced reactive axonal change at both the light and electron microscopic level, the anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase was employed over a 21-day posttraumatic period in selected cerebral and cerebellar efferents coursing through the brain stem. At the designated posttraumatic survival time, the animals were perfused with aldehydes, processed for the light and electron microscopic visualization of the peroxidase reaction product, and examined for any evidence of reactive axonal change. At the 3rd and 4th posttraumatic days, peroxidase-laden swellings could be identified. Some reactive swellings were packed with organelles and were either encompassed by a distended myelin sheath or lacked myelin investment. Other reactive swellings demonstrated either lobulation or increased electron density with macrophage accumulation, all of which indicated degeneration. Wallerian change occurred distal to the reactive swellings; however, with the exception of these changes the related brain parenchyma and vasculature demonstrated no significant abnormality. With continued survival, reactive swellings comparable to those just described were consistently observed; however, now regenerative responses were also seen. At the 5th and 7th days, reactive sprouts were observed originating from reactive swellings which displayed a reduction both in size and in organelle content. By the 9th and 14th posttraumatic days, some sprout-containing swellings demonstrated several robust extensions. These regenerative changes were seen in both myelin- and nonmyelin-invested swellings and persisted through the 21st day, occurring in concert with lobulated, electron dense, and unchanged, swollen reactive axons. This study suggests that head injury elicits axonal swelling that may persist unchanged, degenerate, or undergo a regenerative response. The sustained regenerative responses are considered intriguing and may have relevance both for head-injured humans and for future studies of central nervous system regeneration.