Endogenous Neuronal Replacement in the Juvenile Brain Following Cerebral Ischemia.
Endogenous Neuronal Replacement in the Juvenile Brain Following Cerebral Ischemia.
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DOI：
10.1016/j.neuroscience.2018.03.045
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发表时间：
2018-06-01
期刊：
影响因子：
3.3
通讯作者：
Herson PS
中科院分区：
文献类型：
--
作者：
Rodgers KM;Ahrendsen JT;Patsos OP;Strnad FA;Yonchek JC;Traystman RJ;Macklin WB;Herson PS
通过增强的内源性神经发生或干细胞治疗，替换缺血后死亡的神经元已被长期寻求。不幸的是，虽然各种增强神经发生或干细胞疗法的疗法在动物模型中已被证明是有益的，但它们都未能真正取代缺血核心中的死亡神经元以促进长期恢复。值得注意的是，我们观察到强大的再生中型棘神经元内的缺血核心的幼年小鼠实验性中风。尽管广泛的神经元细胞死亡的青少年和成年人在急性缺血后的时间点（24小时和7天），成熟的新生神经元取代失去的纹状体神经元缺血后30天。这种神经元再增殖只在青少年中发现，而不是成年人，重要的是，伴随着增强缺血后30天的行为恢复。消融神经发生使用辐射防止神经元替代和功能恢复MCAo损伤的幼年小鼠。相比之下，成人的研究结果与以前的报告一致，即新生神经元未能成熟并死亡，几乎没有治疗潜力。这些数据为缺血性卒中后神经元替代和随后的功能恢复提供了支持，并为开发治疗卒中的新疗法提供了新的靶点。
Replacement of dead neurons following ischemia, either via enhanced endogenous neurogenesis or stem cell therapy, has long been sought. Unfortunately, while various therapies that enhance neurogenesis or stem cell therapies have proven beneficial in animal models, they have all uniformly failed to truly replace dead neurons in the ischemic core to facilitate long-term recovery. Remarkably, we observe robust repopulation of medium-spiny neurons within the ischemic core of juvenile mice following experimental stroke. Despite extensive neuronal cell death in the injured striatum of both juveniles and adults at acute time points after ischemia (24hr and 7d), mature newborn neurons replaced lost striatal neurons at 30d post-ischemia. This neuronal repopulation was found only in juveniles, not adults, and importantly, was accompanied by enhanced post-ischemic behavioral recovery at 30d. Ablation of neurogenesis using irradiation prevented neuronal replacement and functional recovery in MCAo-injured juvenile mice. In contrast, findings in adults were consistent with previous reports, that newborn neurons failed to mature and died, offering little therapeutic potential. These data provide support for neuronal replacement and consequent functional recovery following ischemic stroke and new targets in the development of novel therapies to treat stroke.
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影响因子：
5.2
作者：
Achanta, Pragathi;Capilla-Gonzalez, Vivian;Purger, David;Reyes, Juvenal;Sailor, Kurt;Song, Hongjun;Manuel Garcia-Verdugo, Jose;Gonzalez-Perez, Oscar;Ford, Eric;Quinones-Hinojosa, Alfredo
通讯作者：
Quinones-Hinojosa, Alfredo
影响因子：
5.3
作者：
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通讯作者：
Rakic, P
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通讯作者：
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影响因子：
2.9
作者：
MARKGRAF, CG;GREEN, EJ;SCHNEIDERMAN, N
通讯作者：
SCHNEIDERMAN, N
影响因子：
8.3
作者：
Hua, Y;Schallert, T;Xi, GH
通讯作者：
Xi, GH