Sequential Changes in Glial Fibrillary Acidic Protein and Gene Expression Following Parasagittal Fluid-Percussion Brain Injury in Rats

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Abstract
This study documents the regional and temporal patterns of glial fibrillary acidic protein (GFAP) RNA and protein expression after parasagittal fluid-percussion (F-P) brain injury (1.7 to 2.2 atm) in male Sprague-Dawley rats. In situ hybridization was conducted in 28 rats with a 35S-labeled antisense riboprobe to GFAP at 0.5, 2, and 6 hours and 1, 3, and 30 days after traumatic brain injury (TBI) or sham procedures. Immunocytochemical staining of GFAP was conducted in 20 rats at 1, 3, 7, and 30 days after TBI or sham procedures. At 0.5 and 2 hours after TBI, increased GFAP mRNA was restricted to superficial cortical areas underlying the impact site. At 24 hours, increased GFAP mRNA was observed throughout the traumatized hemisphere except within the histopathologically vulnerable lateral parietal cortex and external capsule. Contralateral expression within the hippocampus and cingulate and lateral cortices was also observed. Three days after TBI, GFAP mRNA expression was prominent overlying pial surfaces, in cortical regions surrounding the contusion, and within the hippocampus and lateral thalamus. Immunocytochemical visualization of GFAP at 1 and 3 days demonstrated reactive astrocytes overlying the pial surface, surrounding the cortical contusion, and within ipsilateral white matter tracts, hippocampus, and lateral thalamus. At 30 days, GFAP mRNA and protein expression were present within the deeper cortical layers of the lateral somatosensory cortex and lateral thalamus and throughout ipsilateral white matter tracts. These data demonstrate a complex pattern of GFAP mRNA and protein expression within gray and white matter tracts following F-P brain injury. Patterns of GFAP gene expression may be a sensitive molecular marker for evaluating the global response of the brain to focal injury in terms of progressive neurodegenerative as well as regenerative processes.