Changes in Gene Expression Following Traumatic Brain Injury in the Rat

Abstract

This paper reviews changes in gene expression produced by two rodent models of traumatic brain injury: cortical impact injury and fluid-percussion 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 injury. In addition, AP-1 transcription factor binding is greatly increased in the injured cerebral cortex at 1, 3, and 5 h post-injury. AP-1 binding remains increased for at least 1 day after injury, while SP-1 transcription factor binding activity does not increase. Additional studies have confirmed increases in c-fos mRNA expression in the hippocampus at 30 min, 1 h, and 3 h after injury. These increases in c-fos mRNA 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 fluid-percussion injury, increases in c-fos mRNA can be detected as early as 2 h following injury in the cortex ipsilateral to the site of injury as well as in the hippocampus. Heat-shock protein (hsp72) mRNA is also increased in the ipsilateral cortex and hippocampus following fluid percussion injury. By 24 h post-injury, both c-fos and hsp72 gene expression return to control levels. Severe but not moderate fluid percussion injury produces increased gene expression for glucose-regulated proteins (grp78, grp94) 12 h following injury. Fluid-percussion injury also produces significant increases in expression of both interleukin-1β and tumor necrosis factor-α in the injured cortex and ipsilateral hippocampus as early as 1 h post-injury, that remains elevated up to 6 h in the injured cortex and hippocampus. Key words: brain injury; gene expression; immediate early genes; cytokines