Recruitment of inflammatory cells is known to drive the secondary damage cascades that are common to injuries of the central nervous system (CNS). Cell activation and infiltration to the injury site is orchestrated by changes in the expression of chemokines, the chemoattractive cytokines. Reducing the numbers of recruited inflammatory cells by the blocking of the action of chemokines has turned out be a promising approach to diminish neuroinflammation and to improve tissue preservation and neovascularization. In addition, several chemokines have been shown to be essential for stem/progenitor cell attraction, their survival, differentiation and cytokine production. Thus, chemokines might indirectly participate in remyelination, neovascularization and neuroprotection, which are important prerequisites for CNS repair after trauma. Moreover, CXCL12 promotes neurite outgrowth in the presence of growth inhibitory CNS myelin and enhances axonal sprouting after spinal cord injury (SCI). Here, we review current knowledge about the exciting functions of chemokines in CNS trauma, including SCI, traumatic brain injury and stroke. We identify common principles of chemokine action and discuss the potentials and challenges of therapeutic interventions with chemokines.

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Transplanted stem cells provide beneficial effects on regeneration/recovery after spinal cord injury (SCI) by the release of growth-promoting factors, increased tissue preservation, and provision of a permissive environment for axon regeneration. A rise in chemokine stromal cell-derived factor 1 (SDF-1/CXCL12) expression levels in central nervous system (CNS) injury sites has been shown to play a central role in recruiting transplanted stem cells. Although technically more challenging, it has been shown that after SCI few endogenous stem cells are recruited via SDF-1/CXCR4 signaling. Evidence is accumulating that increasing SDF-1 levels at the injury site (e.g., by exogenous application or transfection methods) further enhances stem cell recruitment. Moreover, SDF-1 might, in addition to migration, also influence survival, proliferation, differentiation, and cytokine secretion of stem cells. Here, we discuss the experimental data available on the role of SDF-1 in stem and progenitor cell biology following CNS injury and suggest strategies for how manipulation of the SDF-1 system could facilitate stem cell-based therapeutic approaches in SCI. In addition, we discuss challenges such as how to circumvent off-target effects in order to facilitate the transfer of SDF-1 to the clinic.

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