Neuroprotective effect of histone deacetylases inhibitor MS-275 following traumatic brain injury in rats

Objective To evaluate the neuroprotective benefits of histone deacetylases (HDAC)inhibitor MS-275 in rats with moderate traumatic brain injury (TBI).Methods Sixty-eight adult male SD rats were assigned to sham injury + placebo treatment (control group),TBI + placebo treatment (injury group),TBI + MS-275 (15 mg/kg) treatment (treatment group Ⅰ) and TBI + MS-275 (45 mg/kg)treatment (treatment group Ⅱ) according to the random number table.An experimental model of moderate TBI in the rat was induced using a lateral fluid percussion device.MS-275 was dissolved in DMSO and administered (15 and 45 mg/kg) intraperitoneally in seven consecutive days(once a day).The first administration was done in 30 minutes postinjury.Alteration in body weight of rats in each group was recorded after injury.Spatial learning and memory retention in rats was assessed using the Morris Water Maze in days 10-14 after TBI.Brain tissues were sectioned to measure acetyl-histone H3 and neuronal survivals in the hippocampus CA2-3 region using immunohistochemistry and cresyl-violet staining techniques.Results TBI rats showed significant body weight loss in 3 days postinjury as compared with the controls (P ＜0.05) and then gradually gained the body weight in 4-5 days postinjury.No significant difference in actual body weight loss after injury was found among injury group and treatment groups (F =0.149,P ＞0.05).Behavioral result revealed that the animals in treatment groups had significant improvement in cognitive performance as compared with injury group (P ＜ 0.01).Immunohistochemical results presented a markedly increased level of acetyl-histone H3 in both treatment groups,with no significant difference as compared with control group and a trend of increase in the survived neurons in the CA2-3 hippocampus in 14 days postinjury (P ＞ 0.05).Conclusions MS-275 achieves visible improvement of acetyl-histone H3 level and cognitive performance in the acute phase of TBI.Simultaneously,this treatment has an ameliorative effect on pathological changes associated with TBI as well and provides a neuroprotective effect against TBI. Key words: Craniocerebral trauma;  Hippocampus ;  Histone deacetylase