Department of Neurology, Central Hospital of Baoji, Baoji.
Department of Neurology, First Affiliated Hospital of Xi'an Jiao Tong University, Xian, Shanxi Province.
Neuroreport. 2021 Apr 7;32(6):489-497. doi: 10.1097/WNR.0000000000001614.
Intracerebral hemorrhage (ICH) is associated with high rate of mortality and morbidity, but lacks effective therapies. Accumulating studies indicated that the hippocampal neurogenesis plays an essential role in the recovery of neurological function after ICH. The Notch1 signaling pathway shows important roles in neurogenesis. However, the effects of Notch1 on the recovery of neurological function after ICH remain unclear. Here, we used ICH mice model to investigate whether Notch1 signaling was involved in the hippocampal neurogenesis and the recovery of neurological function post-ICH. Our results showed that the rate of symmetric division pattern of hippocampal neural stem cells (NSCs) decreased significantly at 3 days after ICH. Meanwhile, the expression of Notch1 in the hippocampus also was reduced significantly. However, Notch1 activator treatment enhanced the expression of Notch1 and increased the number of Sox2+GFAP+ cells. Further, the rate of symmetric division pattern of NSCs also increased after Notch1 activator treatment in mice with ICH. Importantly, the number of DCX+ cells and BrdU+NeuN+ in hippocampus were increased on 28 days post-ICH as the Notch1 expression was upregulated. The motor function and spatial memory ability in post-ICH mice following Notch1 activator treatment also were improved. Taken together, our results suggested that Notch1 signaling could influence the recovery of long-term neurological function by regulating the proliferation and differentiation of the hippocampal NSCs in mice after ICH. Our study may provide ideas for the improvement of neurological function and spatial memory defects after ICH.
脑出血（ICH）的死亡率和发病率高，但缺乏有效的治疗方法。越来越多的研究表明，海马神经发生在 ICH 后神经功能的恢复中起着至关重要的作用。Notch1 信号通路在神经发生中起重要作用。然而，Notch1 对 ICH 后神经功能恢复的影响尚不清楚。在这里，我们使用 ICH 小鼠模型来研究 Notch1 信号是否参与了 ICH 后海马神经发生和神经功能的恢复。我们的结果表明，ICH 后 3 天，海马神经干细胞（NSCs）的对称分裂模式率显著降低。同时，海马 Notch1 的表达也明显降低。然而，Notch1 激活剂治疗可增强 Notch1 的表达，增加 Sox2+GFAP+细胞的数量。进一步的，在 ICH 小鼠中 Notch1 激活剂治疗后，NSCs 的对称分裂模式率也增加。重要的是，随着 Notch1 表达的上调，海马中 DCX+细胞和 BrdU+NeuN+的数量在 ICH 后 28 天增加。经 Notch1 激活剂治疗后，ICH 小鼠的运动功能和空间记忆能力也得到改善。总之，我们的研究结果表明，Notch1 信号可以通过调节 ICH 后小鼠海马 NSCs 的增殖和分化来影响长期神经功能的恢复。我们的研究可能为改善 ICH 后神经功能和空间记忆缺陷提供思路。
