The relationship between SDF-1alpha/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-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.


METHODS
We 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.


RESULTS
SDF-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.


CONCLUSIONS
These 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.
Itoh
Tatsuki
T
Department of Pathology, Kinki University School of Medicine, Osaka, Japan. tatsuki@med.kindai.ac.jp
Satou
Takao
T
Ishida
Hiroyuki
H
Nishida
Shozo
S
Tsubaki
Masahiro
M
Hashimoto
Shigeo
S
Ito
Hiroyuki
H
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D012333:RNA, Messenger; D019718:Receptors, CXCR4