72-KDA HEAT-SHOCK-PROTEIN AND MESSENGER-RNA EXPRESSION AFTER CONTROLLED CORTICAL IMPACT INJURY WITH HYPOXEMIA IN RATS

As part of the stress response, the 72 kDa heat shack protein (hsp72) is induced in neurons after ischemic and traumatic brain injury (TBI). To examine the stress response after TBI with secondary insult, we ex amined the regional and cellular expression of hsp72 mRNA and protein after controlled cortical impact (CCI) injury with secondary hypoxemia and mild hypotension in rats. Rats were killed at 6, 8, 24, 72, or 16 8 h after trauma. Naive and sham-operated rats were used as controls. Brains were removed, and in situ hybridization (n = 2/group), immunocy tochemistry (n = 4/group), and Western blot analysis (n = 3 to 5/group ) for hsp72 was performed. Hsp72 mRNA was expressed in neurons in the ipsilateral cortex, CA3 region of the hippocampus, hilus, and dentate gyrus at 6 h. Hsp72 mRNA was expressed primarily in the ipsilateral co rtex, at 24 h, and by 72 h hsp72 mRNA expression returned to near basa l levels. Hsp72 protein was seen in ipsilateral cortical neurons, hila r neurons, and neurons in the medial aspect of the CA3 region of the h ippocampus (CA3-c) at 24 h. At 72 h, hsp72 immunoreactivity was reduce d versus 24 h in these same regions, but it was increased versus basel ine. Western blot analysis confirmed an increase in hsp72 protein in t he ipsilateral cortex. The regional pattern of hsp72 mRNA induction in neurons was similar to the pattern of protein expression after CCI, w ith the exceptions that hsp72 mRNA, but not protein, was expressed in the dentate gyrus and the lateral aspect of the CA3 region of the hipp ocampus (CA3-a). The stress response, as detected by hsp72 expression, is induced in some neurons in some regions that are selectively vulne rable to delayed neuronal death in this model of TBI. The failure to t ranslate some proteins including hsp72 may be associated with delayed neuronal death in certain hippocampal regions after TBI.