The relationship between SDF-1α/CXCR4 and neural stem cells appearing in damaged area after traumatic brain injury in rats

Objective: The actual relationship between neural stem cells and SDF-1 alpha/CXCR4 after brain injury has not yet been elucidated, although recent studies have speculated that stromal cell-derived factor-1 alpha (SDF-1 alpha) and its receptor, CXCR4, could contribute to neural stem cells migration after brain injury. In the present study, the temporal relationship between neural stem cells (NSCs) and SDF-1 alpha/CXCR4 around a damaged area was investigated using a rat traumatic brain injury (TBI) model. Methods: We used molecular biology techniques and immunohistochemistry to investigate the relationship between SDF-1 alpha/CXCR4 expression and NSCs existence around a damaged area after TBI in the rat brain. Results: SDF-1 alpha mRNA expression and SDF-1 alpha protein synthesis did not increase after TBI. However, SDF-1 alpha leaked from the injured area and diffused into the cortex 1-3 days after TBI. Subsequently, the levels of CXCR4 mRNA expression and CXCR4 protein synthesis increased significantly. Many small cells with a nestin-positive cytoplasm and fibers also showed immunopositivity for both CXCR4 and SOX-2, but not for GFAP, 3-7 days after TBI. Moreover, a proportion of the CXCR4-positive cells and fibers also showed immunostaining for neurofilaments. Discussion: These results suggest that the leaked SDF-1 alpha attracted CXCR4-positive NSCs as well as elongated nerve fibers. It is considered that the SDF-1 alpha/CXCR4 system in the brain contributes to neural stem cells appearance and maturation after TBI. Therefore, exploitation of the SDF-1 alpha/CXCR4 system around a damaged area may improve the brain dysfunction after TBI. [Neurol Res 2009; 31: 90-102]