PROGRESSIVE ATROPHY AND NEURON DEATH FOR ONE-YEAR FOLLOWING BRAIN TRAUMA IN THE RAT

Although atrophic changes have been well described following traumatic brain injury (TBI) in humans, little is known concerning the mechanis ms or progression of brain tissue loss. In the present study, we evalu ated the temporal profile of histopathological changes following paras agittal fluid-percussion (FP) brain injury in rats over 1 year postinj ury. Anesthetized 3-4 month-old Sprague-Dawley Rats (n = 51) were subj ected to FP brain injury of high severity (2.5-2.9 atm, n = 51) or sha m treatment (n = 27). At 1 h, 2 h, 48 h, 1 week, 2 weeks, 1 month, 2 m onths, 6 months and 1 year after brain injury or sham treatment, these animals were humanely euthanized. Brain sections were analyzed with i mage-processing techniques to determine the extent of cortical tissue loss and shrinkage of the hippocampal pyramidal cell layer. In additio n, cell counting was performed to determine the number of neurons in t he dentate hilus of the hippocampus, and glial fibrillary acidic prote in (GFAP) immunostaining was used to reveal reactive astrocytosis. Exa mination of the injured brains revealed substantial and progressive ti ssue loss with concomitant ventriculomegaly in the hemisphere ipsilate ral to injury. The regions with the most notable progressive atrophy i ncluded the cortex, hippocampus, thalamus, and septum. Quantitative an alysis demonstrated a significantly progressive loss of cortical tissu e as well as shrinkage of the hippocampal pyramidal cell layer ipsilat eral to injury over 1 year following injury. In addition, reactive ast rocytosis in regions of atrophy and progressive bilateral death of neu rons in the dentate hilus was observed for 1 year following injury. Th ese results suggest that a chronically progressive degenerative proces s may be initiated by brain trauma. Thus, there is a temporally broad window within which to introduce novel therapeutic strategies designed to ameliorate the short and long-term consequences of brain trauma.