Heavy neurofilament accumulation and α-spectrin degradation accompany cerebellar white matter functional deficits following forebrain fluid percussion injury

Abstract

Evidence for diffuse traumatic axonal injury (TAI) in clinical cases and animal models of traumatic brain injury (TBI) indicate that pathophysiological mechanisms extend to regions remote from the injury epicenter. The potential for indirect cerebellar trauma contributing to TBI pathophysiology is of significance since impairment of motor function and coordination is a common consequence of TBI but is also a domain associated with cerebellar function. The relationship between cerebellar white matter structure and function following traumatic head injury has not been examined. Using the fluid percussion injury (FPI) device applied unilaterally in the forebrain, evoked compound action potential (CAP) recordings from cerebellar white matter of Sprague-Dawley rats indicated a spatial and temporal pattern of electrophysiological deficits throughout the cerebellar vermis. The posterior and middle lobules of the cerebellum exhibited significant declines in evoked CAP amplitude compared to sham controls (p = 0.004, p = 0.005, respectively). Duration of the CAP decay also increased, suggesting that functional white matter deficits were a combination of axonal loss and compromised axonal integrity. Functional white matter deficits persisted at 14 days post-injury in the posterior and middle regions of the cerebellum. Evidence of heavy chain neurofilament (NF200) degradation was observed at 1 day post-injury by Western blot. Immunohistochemistry labeling for NF200 indicated the presence of highly immunoreactive NF200 axonal swellings consistent with morphological features of TAI. α-Spectrin degradation was also observed between 1 and 14 days post-injury. This study demonstrates the electrophysiological consequences of cerebellar white matter injury and a temporal profile of NF200 and spectrin degradation following forebrain FPI. © 2006 Elsevier Inc. All rights reserved.