The protective effect of simvastatin in the acute phase of experimental head trauma

Background and Aim: Traumatic brain injury involves both primary and secondary mechanisms of injury. Secondary injury occurs in the hours to days following the primary insult and is typified by many of physiopathological mechanisms. Previous studies suggested that statins have pleiotropic effects, that are independent of their capability to lower cholesterol such as anti-inflammatory, and anti-oxidative effects. In our study, we performed to assess the neuroprotective role of a single low-dose simvastatin treatment in brain tissue of rats subjected to closed head trauma when given in acute phase of the trauma.Methods: Adult male Wistar rats were divided into four groups as sham, trauma, trauma with vehicle, trauma with simvastatin. Simvastatin was injected intraperitoneally at a dose of 1 mg/kg three hours after the experimental trauma. After 24 hours, intracardiac blood samples were obtained under anesthesia and than animals were sacrified; brains were collected for biochemical and histopathological analyses. Malondialdehyde, vascular endothelial growth factor and total antioxidant status levels were measured in the serum. In the tissue homogenates malondialdehyde, vascular endothelial growth factor, nitric oxide, total antioxidant status levels and superoxide dismutase activity were measured.Results: Upon histopathological evaluation; simvastatin reduced neuropathological changes in comparison with trauma grup. Traumatic brain injury induced a significant increase in malondialdehyde, vascular endothelial growth factor and nitric oxide levels (p<0.05) in brain tissue. Simvastatin treatment markedly reduced malondialdehyde, vascular endothelial growth factor and nitric oxide levels (p<0.05). Simvastatin increased total antioxidant status levels and superoxide dismutase activity in comparison with trauma group, but the differences were not statistically significant.Conclusion: The results of our study suggest that, single low- dose simvastatin treatment reduced neuropathological and biochemical alterations such as lipid peroxidation, cerebral edema formation, pathological angiogenesis and inflammatory response in acute traumatic brain injury and it may be protective against secondary traumatic brain injury. Therefore simvastatin may provide a useful therapeutic option in humans for acute traumatic brain injury.