The effect of simvastatin treatment on proliferation and differentiation of neural stem cells after traumatic brain injury.

Abstract Objective To study the effect of simvastatinon neurological functional recovery after traumatic brain injuries (TBI) and the possible molecular mechanisms, we evaluated simvastatin-induced proliferation and differentiation of neural stem cells(NSCs) in vitro and in vivo and possible involvement of Notch-1signaling in this process. Methods Adult Wistar rats were randomly divided into three groups ( n =28 for each): sham group, saline-treated group and simvastatin-treated group. Simvastatinwas given orally at a dose of 1 mg/kg/day starting at day 1 after TBI. At 1, 3, 7, 14, 21, 28, and 35 days after simvastatintreatment, functional outcome was measured using modified neurological severity scores (mNSS). Immunofluorescence of nestinwas used to identify neurogenesisof NSCs in injured area of TBI rats. Western blot was applied to detect the expression level of Notch-1protein in TBI rats with simvastatin. Results Immunostaining showed a significant increase in the number of nestin-positive cells in injured area of the simvastatin-treated group compared to that of the saline-treated group ( p p Conclusion Simvastatintreatment enhanced neurological functional recovery after TBI possibly via activation of Notch signaling and increasing neurogenesisin the injured area.