CHANGES IN GENE-EXPRESSION FOLLOWING TRAUMATIC BRAIN INJURY IN THE RAT

This paper reviews changes in gene expression produced by two rodent m odels of traumatic brain injury: cortical impact injury and fluid-perc ussion injury. Cortical impact injury produces transient increases in c-fos mRNA expression, which begin as early as 5 min after injury and subsides by 1 day after injury in the cerebral cortex ipsilateral to i njury. In addition, AP-1 transcription factor binding is greatly incre ased in the injured cerebral cortex at 1, 3, and 5 h post-injury. AP-1 binding remains increased for at least I day after injury, while SP-1 transcription factor binding activity does not increase. Additional s tudies have confirmed increases in c-fos mRNA expression in the hippoc ampus at 30 min, 1 h, and 3 h after injury. These increases in c-fos m RNA in the hippocampus preceded increased levels of NGF mRNA that were detected at 1 and 3 h but not at 30 min following injury. Following f luid-percussion injury, increases in c-fos mRNA can be detected as ear ly as 2 h following injury in the cortex ipsilateral to the site of in jury as well as in the hippocampus. Heat-shock protein (hsp72) mRNA is also increased in the ipsilateral cortex and hippocampus following fl uid percussion injury. By 24 h post-injury, both c-fos and hsp72 gene expression return to control levels. Severe but not moderate fluid per cussion injury produces increased gene expression for glucose-regulate d proteins (grp78, grp94) 12 h following injury. Fluid-percussion inju ry also produces significant increases in expression of both interleuk in-1 beta and tumor necrosis factor-alpha in the injured cortex and ip silateral hippocampus as early as 1 h post-injury, that remains elevat ed up to 6 h in the injured cortex and hippocampus.