This project is designed to investigate the efficacy of combination treatment of marrow stromal cells (MSCs) and statins (simvastatin) in improving functional outcome after traumatic brain injury (TBI). Our previous studies have shown that MSCs have a beneficial effect after TBI in rats. To augment the therapeutic benefit of MSCs a combination therapy of MSCs with simvastatin has been designed. Female Wistar rats will be injured using the controlled cortical impact model of head trauma. After injury, simvastatin will be administered orally, and MSCs harvested from male adult rats will be injected into the tail vein of the rats. To compare the efficacy of combination treatment (MSC + simvastatin) with MSC and simvastatin monotherapies other group of rats will be administered either MSCs or simvastatin, solely. The functional outcome of rats will be monitored with a battery of tests, and animals will be sacrificed at different time points. Brain sections will be stained with immunohistochemistry and MSCs will be identified by localizing Y chromosomes within them. The induction of brain plasticity with treatment will be measured by studying neurogenesis, synaptogenesis and angiogenesis. In addition, growth factors which are mediators of this plasticity will be measured using enzyme-linked immunosorbent assay (ELISA). If the treatment combining MSCs with simvastatin is found to be more effective than monotherapy, this will increase the clinical relevance of MSC treatment by allowing us to use smaller and safer doses. [unreadable] [unreadable] [unreadable]