Absence of Sema4D improves oligodendrocyte recovery after cerebral ischemia/reperfusion injury in mice
Absence of Sema4D improves oligodendrocyte recovery after cerebral ischemia/reperfusion injury in mice
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DOI：
10.1016/j.neures.2015.12.016
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发表时间：
2016-07-01
影响因子：
2.9
通讯作者：
Inagaki, Shinobu
中科院分区：
文献类型：
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作者：
Wada, Takenobu;Sawano, Toshinori;Inagaki, Shinobu
Sema 4D最初被鉴定为发育过程中轴突导向的负调节因子，参与各种生理和病理反应。在这项研究中，我们评估了Sema 4D缺乏对脑缺血/再灌注后少突胶质细胞恢复的影响，采用直接结扎大脑中动脉再灌注。在Sema 4D（+/+）野生型和Sema 4D（-/-）无效突变小鼠中，在再灌注后3天，梗死周围区域显示少突胶质细胞数量减少。随后，观察到两组中少突胶质细胞的数量逐渐恢复。然而，Sema 4D缺陷小鼠在再灌注第14天和第28天表现出少突胶质细胞的恢复增强和少突胶质细胞祖细胞的上调。与Sema 4D（+/+）小鼠相比，通过掺入溴脱氧尿苷鉴定的细胞增殖在Sema 4D（-/-）小鼠中从再灌注后第3天至第14天增强。此外，与Sema 4D（+/+）小鼠相比，Sema 4D（-/-）小鼠在再灌注后第7天少突胶质细胞的凋亡性细胞死亡减少。这些发现表明，在Sema 4D（-/-）小鼠中，祖细胞增殖和少突胶质细胞存活的增强导致少突胶质细胞恢复的改善。这可能为脑卒中患者的神经修复治疗提供一种新的方法，其目的是操纵内源性少突胶质细胞的生成，从而促进脑卒中后的脑修复。(C)由Elsevier爱尔兰Ltd.出版
Sema4D, originally identified as a negative regulator of axon guidance during development, is involved in various physiological and pathological responses. In this study, we evaluated the effect of Sema4D-deficiency on oligodendrocyte restoration after the cerebral ischemia/reperfusion using direct ligation of the middle cerebral artery followed by reperfusion. In both Sema4D(+/+) wild-type and Sema4D(-/-) null mutant mice, the peri-infarct area showed a decrease in the number of oligodendrocytes at 3 days post-reperfusion. Subsequently, the number of oligodendrocytes was observed to gradually recover in both groups. Sema4D-deficient mice, however, showed an enhanced recovery of oligodendrocytes and an upregulation of oligodendrocyte progenitor cells at days 14 and 28 of reperfusion. Cell proliferation identified by incorporation of bromodeoxyuridine was enhanced in Sema4D(-/-) mice from days 3 to 14 post-reperfusion compared to the Sema4D(+/+) mice. Furthermore, apoptotic cell death of oligodendrocytes was reduced at days 7 post-reperfusion in Sema4D(-/-) mice compared to Sema4D(+/+) mice. These findings indicate that enhanced proliferation of progenitor cells and survival of oligodendrocytes resulted in improved oligodendrocyte recovery in Sema4D(-/-) mice. This may provide a new approach for neurorestorative treatment in patients with stroke, which aims to manipulate endogenous oligodendrogenesis and thereby to promote brain repair after stroke. (C) 2016 Published by Elsevier Ireland Ltd.