• Tatsuki Itoh, Takao Satou, Hiroyuki Ishida, Shozo Nishida, Masahiro Tsubaki, Shigeo Hashimoto, and Hiroyuki Ito.
• Department of Pathology, Kinki University School of Medicine, Osaka, Japan. tatsuki@med.kindai.ac.jp
• Neurol. Res. 2009 Feb 1; 31 (1): 90-102.

ObjectiveThe actual relationship between neural stem cells and SDF-1alpha/CXCR4 after brain injury has not yet been elucidated, although recent studies have speculated that stromal cell-derived factor-1alpha (SDF-1alpha) 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-1alpha/CXCR4 around a damaged area was investigated using a rat traumatic brain injury (TBI) model.MethodsWe used molecular biology techniques and immunohistochemistry to investigate the relationship between SDF-1alpha/CXCR4 expression and NSCs existence around a damaged area after TBI in the rat brain.ResultsSDF-1alpha mRNA expression and SDF-1alpha protein synthesis did not increase after TBI. However, SDF-1alpha 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.DiscussionThese results suggest that the leaked SDF-1alpha attracted CXCR4-positive NSCs as well as elongated nerve fibers. It is considered that the SDF-1alpha/CXCR4 system in the brain contributes to neural stem cells appearance and maturation after TBI. Therefore, exploitation of the SDF-1alpha/CXCR4 system around a damaged area may improve the brain dysfunction after TBI.

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