Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats

Abstract

There is evidence for chronic atrophy after human head trauma, which may be associated with long-term functional deficits. However, using established models of traumatic brain injury (TBI) only limited data are available for clarifying the extent of progressive gray and white matter atrophy. In the present study, male Sprague-Dawley rats underwent moderate (2.01-2.21 atm) parasagittal fluid percussion brain injury (n=7) or sham (n=3) surgery and were killed at 1 year post TBI. Semiserial sections were obtained through the neuraxis and double stained with hematoxylin and eosin to demarcate gray matter structures and Luxol fast blue for white matter visualization. Both ipsilateral and contralateral volume measurements were obtained for the following structures: cerebral cortex, hippocampus, dentate gyrus, thalamus, lateral ventricle, external capsule, internal capsule, cerebral peduncle and corpus callosum. Quantitative assessment of ipsilateral gray matter structures from TBI rats revealed significant reductions in cerebral cortical area measurements posterior from the trauma epicenter compared to sham animals. Importantly, several white matter tracts exhibited dramatic atrophy. A comparison of TBI and sham groups demonstrated a significant (P<0.05) decrease in the external capsule and cerebral peduncle volumes (P<0.007). In addition, there was a significant volume expansion (533% of control) of the ipsilateral lateral ventricle (P<0.03). These novel data emphasize the need to clarify the pathophysiology of progressive white matter damage after TBI and the development of therapeutic strategies to target white matter pathology.