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.
Highlights
Neurologic manifestations are seen among patients with COVID-19.
COVID-19 may attack the brain through hematogenous route or neuronal dissemination.
Neuronal damage is caused either by direct virus effects or by immunopathology.
Forty-two male Wistar rats (200-250 g) were randomly assigned as sham-operated rats (SHAM; n=12), rats subjected to cerebral ischemia (ISC; n=15), and rats with cerebral ischemia that were later treated with CIMT (ISC+CIMT; n=15). All rats were housed under controlled temperature in a 12-hour light/dark cycle with easy access to food and water and assigned to groups with a minimum of 4 animals per enclosure. Protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University (permit No. SCXK [Liao] 2008-0005).Background and Purpose-Constraint-induced movement therapy (CIMT) improves functional outcome in patients with stroke possibly through structural plasticity. We hypothesized that CIMT could enhance axonal growth by overcoming the intrinsic growth-inhibitory signals, leading eventually to improved behavioral performance in stroke rats. Methods-Focal cerebral ischemia was induced by intracerebral injection of endothelin-1. Adult Wistar rats were divided into a sham-operated group, an ischemic group, and an ischemic group treated with CIMT. CIMT started at postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine was injected into the contralateral sensorimotor cortex at postoperative day 14 to trace crossing axons at the cervical spinal cord. The expressions of Nogo-A, Nogo receptor, RhoA, and Rho-associated kinase in the peri-infarct cortex, and the expressions of biotinylated dextran amine, growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated spinal cord were measured by immunohistochemistry and Western blots. Behavioral recovery was analyzed at postoperative days 29 to 32. Results-Infarct volumes were not different between groups after stroke. CIMT significantly increased the length and the number of midline crossings of contralateral corticospinal axons to the denervated cervical spinal cord. CIMT significantly decreased the expressions of Nogo-A/Nogo receptor and RhoA/Rho-associated kinase in the peri-infarct cortex, and increased the expressions of growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated cervical spinal cord. Behavioral performances assessed by the beam-walking test and the water maze test were improved significantly by CIMT. Conclusions-CIMT promoted poststroke synaptic plasticity and axonal growth at least partially by overcoming the intrinsic growth-inhibitory signaling, leading to improved behavioral outcome. (Stroke. 2013;44:1698-1705.)
Stromal cell-derived factor-1 was originally found as a chemoattractant for immune cells. Later it was shown that stromal cell-derived factor-1 and its specific receptor CXCR4 were widely expressed in the developing and mature brains. They participate in a variety of physiological and pathological processes including brain development, angiogenesis, neurodegeneration and neurogenesis. Stromal cell-derived factor-1/CXCR4 plays a particularly important role in adult neurogenesis through mediating the proliferation of neurogenitors, regulating the migration, differentiation, as well as functional integration of newborn neurons into existing networks. After stroke, adult neurogenesis in both the subventricular zone and subgranular zone is robustly increased and stromal cell-derived factor-1 and matrix metalloproteinases are released by damaged tissue. Stromal cell-derived factor-1 promotes the proliferation of neuroblasts and their migration to injured areas. However, the majority of the neuroblasts produced after stroke undergo apoptosis and only a few differentiate and survive in the long-term. The interaction of stromal cell-derived factor-1 and matrix' metalloproteinases may contribute to the unfavorable local microenvironment diminishing the survival of newborn neurons. Stromal cell-derived factor-1/matrix metalloproteinases and their downstream pathways may provide a new target for the treatment of stroke.
Abbreviations
BrdUBromodeoxyuridine DG Dentate gyrus DGCs Dentate granule cells DCX Doublecortin GABA Gamma-aminobutyric-acid
SUMMARYAdult generated neurons in the dentate gyrus become functionally integrated into the existing hippocampal circuit by forming synapses with mature neurons. It is now well established that seizure activity increases neural proliferation, but only recently has the fate of seizure-induced newborn neurons been examined. An emerging consensus proposes that newborn neurons are highly sensitive to their environment, such that synaptic integration is profoundly altered following insults such as seizures. Whether these changes contribute to or counteract epileptogenesis is a subject of great interest because neurogenesis provides a potential target for therapeutic intervention. In this review, we summarize the current understanding of the functional integration of adult generated granule cells in the normal rodent hippocampus, and describe how this process can be altered during epileptogenesis.
Intracerebral hemorrhage (ICH) has the highest mortality rate in all strokes. However, controversy still exists concerning the association between plasma homocysteine (Hcy) and ICH. A systematic review and meta-analysis was conducted using Pubmed, Embase, and Web of Science up to April 18, 2017. Standard mean difference (SMD) for mean differences of plasma Hcy levels with 95% confidence intervals (CI) was calculated. Seven studies including 667 ICH patients and 1821 ischemic stroke patients were identified for meta-analysis. Our results showed that Hcy levels in ICH patients were significantly higher than those in healthy controls (SMD = 0.59, 95% CI = 0.51–0.68, P < 0.001); no statistic differences were found in the comparisons of Hcy levels between ICH and ischemic stroke (SMD = −0.03, 95% CI = −0.13–0.06, P > 0.05); further subgroup analysis of ethnicity (Asians: SMD = 0.57, 95% CI = 0.48–0.66, P < 0.001; Caucasians: SMD = 0.77, 95% CI = 0.51–1.02, P < 0.001) and sample size (small samples: SMD = 0.55, 95% CI = 0.30–0.80, P < 0.001; large samples size: SMD = 0.60, 95% CI = 0.51–0.69, P < 0.001) in relation to Hcy levels between ICH and healthy controls did not change these results. In conclusion, Hcy level may be an aggravating factor in atherosclerosis, which is positively associated with high risk of ICH. Race-specific differences between Asians and Caucasians have no impact on the risk of ICH.
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