RESUMO
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 male rats,weighting 220-250 g,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).Experimental rats were treated with valproic acid (300 mg/kg,twice daily) by intraperitoneal injection.Rat behavioral outcomes were measured 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 infiltration into cerebral cortex were tested with immunohistochemistry staining against ED-1 for macrophage.Inflammatory cytokines (INF-γ,tumor necrosis factor-α,interleukin-6) were measured by Western blotting.The statistical analysis were performed by ANOVA and chi-square tests using the statistical software program SPSS 13.0.Results Compared with the Sham group,the levels of brain edema,mNSS and macrophage cell infiltration were significantly increased after TBI (all P =0.00).The expressions of inflammatory cytokines were also increased significantly (all P =0.00).Compared with the TBI group,TBI + VAP group had significantly lower brain water content[3day:(80.12 ±0.59)％ vs.(82.14 ±0.67)％,P=0.04;7day:(74.74 ±0.72)％ vs.(77.93 ±0.48)％,P=0.01],and mNSS scores [3 day:(10.53 ±0.32) vs.(11.74 ±0.48),P =0.02;7 day:(7.97 ± 0.32) vs.(10.73 ± 0.42),P =0.01].VPA suppressed macrophage cell infiltration into cerebral cortex [(36.44 ± 0.72) ％ vs.(25.93 ± 0.48) ％ P =0.00].Meanwhile,VPA inhibited the expressions of inflammatory cytokines (INF-γ,TNF-α,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.
