Background: Stromal cell-derived factor-1 (SDF1) and its major signaling receptor, CXCR4, were initially described in the immune system; however, they are also expressed in the nervous system, including the spinal cord. After spinal cord injury, the blood brain barrier is compromised, opening the way for chemokine signaling between these two systems. These experiments clarified prior contradictory findings on normal expression of SDF1 and CXCR4 as well as examined the resulting spinal cord responses resulting from this signaling.Methods: These experiments examined the expression and function of SDF1 and CXCR4 in the normal and injured adult mouse spinal cord primarily using CXCR4-EGFP and SDF1-EGFP transgenic reporter mice.Results: In the uninjured spinal cord, SDF1 was expressed in the dorsal corticospinal tract (dCST) as well as the meninges, whereas CXCR4 was found only in ependymal cells surrounding the central canal. After spinal cord injury (SCI), the pattern of SDF1 expression did not change rostral to the lesion but it disappeared from the degenerating dCST caudally. By contrast, CXCR4 expression changed dramatically after SCI. In addition to the CXCR4+ cells in the ependymal layer, numerous CXCR4+ cells appeared in the peripheral white matter and in the dorsal white matter localized between the dorsal corticospinal tract and the gray matter rostral to the lesion site. The non-ependymal CXCR4+ cells were found to be NG2+ and CD11b+ macrophages that presumably infiltrated through the broken blood-brain barrier. One population of macrophages appeared to be migrating towards the dCST that contains SDF1 rostral to the injury but not towards the caudal dCST in which SDF1 is no longer present. A second population of the CXCR4+ macrophages was present near the SDF1-expressing meningeal cells.Conclusions: These observations suggest that attraction of CXCR4+ macrophages is part of a programmed response to injury and that modulation of the SDF1 signaling system may be important for regulating the inflammatory response after SCI.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience