Effect Of Valproic Acid On Inflammatory Response After Traumatic Brain Injury In Rats

Objective To investigate the effects and mechanisms of valproic acid on brain edema, neurobehavioral outcome and inflammatory response after traumatic brain injury(TBI) in rats. Methods TBI animal models were established using Feeney's method. Fifty-four SD rats were randomly divided into 3 groups(n=18): sham operation group(group sham), traumatic brain injury group(group TBI) and valproic acid treatment group(group TBI+VPA). We measured rat behavioral outcomes by modified neurologic severity score(mNSS) tests at day 1, 3, and 7 after TBI. Brain water content was measured with wet-dry weight method. The blood cells infiltrating into cerebral cortex by immunohistochemistry staining against ED-1 for macrophage. Inflammatory cytokines [INF-?, tumor necrosis factor-? TNFa, interleukin-6] were tested with Western blotting. Results Compared with the Sham group, the levels of brain edema, mNSS and macrophage cell infiltrating were significantly increased after TBI(P<0.05). The expressions of Inflammatory cytokines were also increased significantly(P<0.05). Compared with the TBl group, Treatment with VPA reduced brain edema and improved neurobehavioral outcome, especially at day 3(P<0.05). Meanwhile, VPA suppressed macrophage cell infiltrating into cerebral cortex and the expressions of inflammatory cytokines(INF-?, TNFa,IL-6)(P<0.05). Conclusions Treatment with VPA markedly reduced brain edema and improved neurological outcomes after TBI, possibly mediated by inhibited TBI-induced cerebral inflammatory responses and macrophage cell infiltrating into cerebral cortex.