CXCL12 promotes spinal nerve regeneration and functional recovery after spinal cord injury

CXCL12 promotes spinal nerve regeneration and functional recovery after spinal cord injury
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CXCL12促进脊髓损伤后脊髓神经再生和功能恢复

DOI:
10.1097/wnr.0000000000001613
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发表时间:
2021
期刊:
影响因子:
1.7
通讯作者:
Rongqian Wu
Rongqian Wu
中科院分区:
医学4区
文献类型:
--
作者:
Jingyuan Li;Yanqiong Wu;Ping;Xiaoxiao Huang;Yongli Liu;Minjing Peng;Rongqian Wu

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脊髓损伤(SCI)由于外部微环境和内部神经生物化学的复杂机制限制了神经元的可塑性和轴突再生,导致运动和感觉功能的永久性丧失。趋化因子CXCL 12在中枢神经系统发育和疾病修复中具有重要作用。在本研究中,脊髓损伤后CXCL12表达下调。脊髓损伤还引起神经胶质增生和突触丢失。鞘内注射CXCL 12通过诱导神经元连接的形成和抑制胶质瘢痕的形成促进脊髓损伤的功能恢复。为了证实CXCL12是否促进突触形成和功能性神经元连接,用CXCL12肽处理原代皮层神经元,使用免疫荧光染色检查突触,并使用全细胞膜片钳测试突触的功能。结果表明,CXCL 12肽促进轴突伸长、分支形成、树突生成和突触发生。电生理结果表明,CXCL 12肽增加神经元之间的功能连接。总之,本研究阐明了脊髓损伤发生发展的潜在机制,并为促进脊髓损伤后功能恢复提供了一种潜在的方法。
Spinal cord injury (SCI) leads to permanent loss of motor and sensory function due to the complex mechanisms of the external microenvironment and internal neurobiochemistry that restrict neuronal plasticity and axonal regeneration. Chemokine CXCL12 was verified in regulating the development of central nervous system (CNS) and repairing of CNS disease. In the present study, CXCL12 was downregulated in the spinal cord after SCI. SCI also induced gliosis and loss of synapse. Intrathecal treatment of CXCL12 promoted the functional recovery of SCI by inducing the formation of neuronal connections and suppressing glia scar. To confirm whether CXCL12 promoted synapse formation and functional neuronal connections, the primary cortical neurons were treated with CXCL12 peptide, the synapse was examined using Immunofluorescence staining and the function of synapse was tested using a whole-cell patch clamp. The results indicated that CXCL12 peptide promoted axonal elongation, branche formation, dendrite generation and synaptogenesis. The electrophysiological results showed that CXCL12 peptide increased functional connections among neurons. Taken together, the present study illustrated an underlying mechanism of the development of SCI and indicated a potential approach to facilitate functional recovery of spinal cord after SCI.
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