After Intracerebral Hemorrhage, Oligodendrocyte Precursors Proliferate and Differentiate Inside White-Matter Tracts in the Rat Striatum.
After Intracerebral Hemorrhage, Oligodendrocyte Precursors Proliferate and Differentiate Inside White-Matter Tracts in the Rat Striatum.
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DOI：
10.1007/s12975-015-0445-3
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发表时间：
2016-06
影响因子：
6.9
通讯作者：
Schlichter LC
中科院分区：
文献类型：
--
作者：
Joseph MJ;Caliaperumal J;Schlichter LC
髓鞘轴突损伤有助于急性中枢神经系统损伤后的神经功能缺损，包括缺血性和出血性中风。促进再髓鞘形成的潜在治疗将需要完全分化的少突胶质细胞，但脑出血（ICH）后它们的命运几乎一无所知。利用纹状体脑出血大鼠模型，我们量化了血肿周围区域、周围纹状体和对侧纹状体中少突胶质前体细胞（OPCs）（1,3,7,14和28天）的存活、增殖和分化。在血肿周围，Olig2+细胞的密度在前7天急剧增加，这与髓鞘轴突束的紊乱和断裂相吻合。1 ~ 28天，前脑室下区Olig2+细胞的Ki67+增殖很少。然而，到第3天，许多细胞在血肿周围区域增殖，表明局部增殖扩大了它们的数量。14天时，血肿周围区Olig2+细胞密度下降，28天时，对侧纹状体中Olig2+细胞密度降至较低水平。在后来的时间里，许多幸存的轴突排列成白质束，看起来不那么肿胀或破碎。少突胶质细胞成熟在28天内普遍存在。血肿周围未成熟OPCs （NG2+Olig2+）和成熟少突胶质细胞（CC-1+Olig2+）的密度在第一周内显著增加。无论成熟状态如何，它们都优先在白质束内增加。这些结果提供了内源性少突胶质细胞前体在血肿周围区域增殖和分化的证据，并有可能在出血性卒中后轴突束重新形成髓鞘。
Damage to myelinated axons contributes to neurological deficits after acute CNS injury, including ischemic and hemorrhagic stroke. Potential treatments to promote re-myelination will require fully differentiated oligodendrocytes, but almost nothing is known about their fate following intracerebral hemorrhage (ICH). Using a rat model of ICH in the striatum, we quantified survival, proliferation, and differentiation of oligodendrocyte precursor cells (OPCs) (at 1, 3, 7, 14, and 28 days) in the peri-hematoma region, surrounding striatum, and contralateral striatum. In the peri-hematoma, the density of Olig2+ cells increased dramatically over the first 7 days, and this coincided with disorganization and fragmentation of myelinated axon bundles. Very little proliferation (Ki67+) of Olig2+ cells was seen in the anterior subventricular zone from 1 to 28 days. However, by 3 days, many were proliferating in the peri-hematoma region, suggesting that local proliferation expands their population. By 14 days, the density of Olig2+ cells declined in the peri-hematoma region, and, by 28 days, it reached the low level seen in the contralateral striatum. At these later times, many surviving axons were aligned into white-matter bundles, which appeared less swollen or fragmented. Oligodendrocyte cell maturation was prevalent over the 28-day period. Densities of immature OPCs (NG2+Olig2+) and mature (CC-1+Olig2+) oligodendrocytes in the peri-hematoma increased dramatically over the first week. Regardless of the maturation state, they increased preferentially inside the white-matter bundles. These results provide evidence that endogenous oligodendrocyte precursors proliferate and differentiate in the peri-hematoma region and have the potential to re-myelinate axon tracts after hemorrhagic stroke.