Netrin-1 Overexpression Promotes White Matter Repairing and Remodeling after Focal Cerebral Ischemia in Mice

He, Xiaosong; Li, Yaning; Lu, Haiyan; Zhang, Zhijun; Wang, Yongting; Yang, Guo‐Yuan

doi:10.1038/jcbfm.2013.150

Cited by 48 publications

(42 citation statements)

References 38 publications

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“…These alterations have direct and/or indirect effects on neurons and other glial cell populations during and after ischemia. By overexpression of Netrin‐1 or CXCL12 gene in OPCs, studies showed those factors promote OPCs proliferation, migration, axon remyelination, further facilitating white matter repair and remodeling, which provides a therapeutic perspective for targeting NG2‐glia in ischemia . These conclusions, however, need to be further confirmed in vivo.…”

Section: Discussionmentioning

confidence: 99%

Roles of NG2‐glia in ischemic stroke

et al. 2017

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Recent studies have shown that a widely distributed class of glial cells, termed NG2-glia, engages in rapid signaling with surrounding neurons through direct synaptic contacts in the developing and mature central nervous system (CNS). This unique glial cell group has a typical function of proliferating and differentiating into oligodendrocytes during early development of the brain, which is crucial to axon myelin formation. Therefore, NG2-glia are also called oligodendrocyte precursor cells (OPCs). In vitro and in vivo studies reveal that NG2-glia expressing receptors and ion channels demonstrate functional significance for rapid signaling with neuronal synapses and modulation of neuronal activities in both physiological and pathological conditions. Although it is well known that NG2-glia play an important role in demyelinating diseases such as multiple sclerosis, little is known about how NG2-glia or OPCs impact neurons and brain function following ischemic injury. This review summarizes recent progress on the roles of NG2-glia in ischemic stroke and illustrates new approaches for targeting NG2-glia in the brain to treat this disease.

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Section: Discussionmentioning

confidence: 99%

Roles of NG2‐glia in ischemic stroke

et al. 2017

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“…MBP staining intensity was computed as the mean integrated optical density (IOD), as previously described [23]. In brief, microphotographs were taken using a ×5 objective lens (DM2500; Leica Microsystems).…”

Section: Methodsmentioning

confidence: 99%

CXCL12Gene Therapy Ameliorates Ischemia-Induced White Matter Injury in Mouse Brain

Tang

Liu

et al. 2015

Stem Cells Translational Medicine

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Remyelination is an important repair process after ischemic stroke-induced white matter injury. It often fails because of the insufficient recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to oligodendrocytes. We investigated whether CXCL12 gene therapy promoted remyelination after middle cerebral artery occlusion in adult mice. The results showed that CXCL12 gene therapy at 1 week after ischemia could protect myelin sheath integrity in the perifocal region, increase the number of platelet-derived growth factor receptor-a (PDGFRa)-positive and PDGFRa/bromodeoxyuridine-double positive OPCs in the subventricular zone, and further enhance their migration to the ischemic lesion area. Coadministration of AMD3100, the antagonist for CXCL12 receptor CXCR4, eliminated the beneficial effect of CXCL12 on myelin sheath integrity and negatively influenced OPC proliferation and migration. At 5 weeks after ischemia, CXCR4 was found on the PDGFRa-and/or neuron/glia type 2 (NG2)-positive OPCs but not on the myelin basic protein-positive mature myelin sheaths, and CXCR7 was only expressed on the mature myelin sheath in the ischemic mouse brain. Our data indicated that CXCL12 gene therapy effectively protected white matter and promoted its repair after ischemic injury. The treatment at 1 week after ischemia is effective, suggesting that this strategy has a longer therapeutic time window than the treatments currently available. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1122-1130 SIGNIFICANCEThis study has demonstrated for the first time that CXCL12 gene therapy significantly ameliorates brain ischemia-induced white matter injury and promotes oligodendrocyte progenitor cell proliferation in the subventricular zone and migration to the perifocal area in the ischemic mouse brain. Additional data showed that CXCR4 receptor plays an important role during the proliferation and migration of oligodendrocyte progenitor cells, and CXCR7 might play a role during maturation. In contrast to many experimental studies that provide treatment before ischemic insult, CXCL12 gene therapy was performed 1 week after brain ischemia, which significantly prolonged the therapeutic time window of brain ischemia.

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“…Under pathological conditions, Netrin-1 inhibits inflammation and apoptosis, as well as promotes repair after ischemic stroke by increasing angiogenesis (Lu et al, 2012; Rosenberger et al, 2009; Sun et al, 2011). Overexpression of Netrin-1 increases proliferation and differentiation of OPC into mature oligodendrocytes, and promotes white matter remyelination and neurobehavioral outcomes after focal cerebral ischemia in mice (He et al, 2013). …”

Section: Molecular Pathways Involved In Ischemic White Matter Damamentioning

confidence: 99%

The axon–glia unit in white matter stroke: Mechanisms of damage and recovery

Rosenzweig

Carmichael

2015

Brain Research

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Approximately one quarter of all strokes in humans occur in white matter, and the progressive nature of white matter lesions often results in severe physical and mental disability. Unlike cortical grey matter stroke, the pathology of white matter stroke revolves around disrupted connectivity and injured axons and glial cells, rather than neuronal cell bodies. Consequently, the mechanisms behind ischemic damage to white matter elements, the regenerative responses of glial cells and their signaling pathways, all differ significantly from those in grey matter. Development of effective therapies for white matter stroke would require an enhanced understanding of the complex cellular and molecular interactions within the white matter, leading to the identification of new therapeutic targets. This review will address the unique properties of the axon-glia unit during white matter stroke, describe the challenging process of promoting effective white matter repair, and discuss recently-identified signaling pathways which may hold potential targets for repair in this disease.

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Netrin-1 Overexpression Promotes White Matter Repairing and Remodeling after Focal Cerebral Ischemia in Mice

Cited by 48 publications

References 38 publications

Roles of NG2‐glia in ischemic stroke

Roles of NG2‐glia in ischemic stroke

CXCL12Gene Therapy Ameliorates Ischemia-Induced White Matter Injury in Mouse Brain

The axon–glia unit in white matter stroke: Mechanisms of damage and recovery

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