The Role of SDF-1/CXCR4/CXCR7 in Neuronal Regeneration after Cerebral Ischemia

Abstract

Stromal cell-derived factor-1 is a chemoattractant produced by bone marrow stromal cell lines. It is recognized as a critical factor in the immune and central nervous systems (CNSs) as well as exerting a role in cancer. SDF-1 activates two G protein-coupled receptors, CXCR4 and CXCR7; these are expressed in both developing and mature CNSs and participate in multiple physiological and pathological events, e.g., inflammatory response, neurogenesis, angiogenesis, hematopoiesis, cancer metastasis, and HIV infection. After an ischemic stroke, SDF-1 levels robustly increase in the penumbra regions and participate in adult neural functional repair. Here we will review recent findings about SDF-1 and its receptor, analyse their functions in neurogeneration after brain ischemic injury: i.e., how the system promotes the proliferation, differentiation and migration of neural precursor cells and mediates axonal elongation and branching.

Loss of Cxcr5 alters neuroblast proliferation and migration in the aged brain

“…Cxcl12 is expressed by endothelial cells and neuronal precursors in SVZ, and has been shown to promote proliferation and migration of neuroblasts. 42 Supporting the idea of Cxcl12 as responsible for the increased migration out of the SVZ, Cxcl12 have been shown to increase migration of T-cells and HeLa cells even in the absence of a concentration gradient. 43,44 Therefore, a plausible explanation for our findings is that loss of Cxcr5 leads to increased systemic levels of IL-6, which together with increased Cxcl12 expression in the SVZ promote neuroblast proliferation and their migration out of the SVZ.…”

<p>The Clinical Effect of Electroconvulsive Therapy and Its Relationship with Serum Levels of MMP-9 and CXCL12 in Patients with Mania</p>

“…CXCL12 and its cognitive receptor CXCR4 are expressed by neural stem cells are involved in adult neurogenesis. 32 Enhanced environment induces neuronal plasticity and hippocampal neurogenesis which is accompanied by was accompanied by the increased expressions of SDF-1 and CXCR4 in the hippocampus, 33 indicating that CXCL12 is a neurogenesis inducer factor. This notion was supported by another observation which demonstrated that CXCR4 antagonist, AMD3100 reversed the effect of EE on neurogenesis.…”

Intraventricular CXCL12 is neuroprotective and increases neurogenesis in a murine model of stroke

“…CXCR4 is found at the membrane of a variety of cells including neurons, astrocytes, microglia, bone marrow-derived cells, and NSCs (Wang et al 2012). CXCL12 and CXCR4 are constitutively expressed in the brain but are up-regulated in the ischemic penumbra regions following ischemic stroke (Cheng et al 2017b). CXCL12/CXCR4 is thought to play important roles in multiple processes after ischemic stroke, which include inflammatory response, angiogenesis, and the recruitment of bone marrow-stem cells and NSCs to injury (Kokovay et al 2010;Yellowley 2013).…”

“…CXCR7 affinity for CXCL12 is almost 10 times higher than for CXCR4 and is more distributed in neurons (Cheng et al 2017b). The pathways behind their role are not completely understood.…”

“…CXCR7 was thought to function as a scavenger receptor that can regulate the extracellular availability of CXCL12, mediating its internalization and subsequent lysosomal degradation (Boldajipour et al 2008;Sánchez-Alcañiz et al 2011). Clarification of the role of CXCR7 will be required in the future (Cheng et al 2017b). However, lack of a commercial CXCR7 antagonist difficult this process.…”