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

Abstract

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.

DISCUSSION:

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.

• Authors: Tatsuki Itoh, Takao Satou, Hiroyuki Ishida, Shozo Nishida, Masahiro Tsubaki, Shigeo Hashimoto, Hiroyuki Ito
• Journal: Neurological research (Neurol Res) Vol. 31 Issue 1 Pg. 90-102 (Feb 2009) ISSN: 0161-6412 [Print] England
• PMID: 19228460 (Publication Type: Journal Article)

Chemical References

• Chemokine CXCL12
• Cxcr4 protein, rat
• RNA, Messenger
• Receptors, CXCR4

Topics

• Animals
• Brain Injuries (metabolism, pathology)
• Chemokine CXCL12 (biosynthesis)
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique
• Immunohistochemistry
• Male
• Neurogenesis (physiology)
• Neurons (cytology, metabolism)
• RNA, Messenger (analysis)
• Rats
• Rats, Wistar
• Receptors, CXCR4 (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Stem Cells (cytology, metabolism)