Hu Xvlei, Zhang Yifan, Wang Lei, Ding Jiangwei, Li Mei, Li Hailiang, Wu Liang, Zeng Zhong, Xia Hechun
Department of Neurosurgery, Shanxi Provincial People's Hospital, Taiyuan, China.
School of Clinical Medicine, Ningxia Medical University, Yinchuan, China.
Front Cell Neurosci. 2022 Oct 20;16:956079. doi: 10.3389/fncel.2022.956079. eCollection 2022.
Spinal cord injury (SCI) is a traumatic event that can lead to neurodegeneration. Neuronal damage in the primary motor cortex (M1) can hinder motor function recovery after SCI. However, the exact mechanisms involved in neuronal damage after SCI remain incompletely understood. In this study, we found that microglia were activated in M1 after SCI, which triggered Nod-like receptor protein 3 (NLRP3) related chronic neuroinflammation and neuronal damage . Meanwhile, treatment with the microglia inhibitor minocycline reduced inflammation-induced neuronal damage in M1, protected the integrity of the motor conduction pathway, and promoted motor function recovery. Furthermore, we simulated chronic inflammation in M1 after SCI by culturing the primary neurons in primary microglia-conditioned medium, and observed that the injury to the primary neurons also occurred ; however, as observed , these effects could be mitigated by minocycline treatment. Our results indicated that microglial activation in M1 mediates NLRP3-related neuroinflammation and causes the injury to M1 neurons, thereby impairing the integrity of the motor conduction pathway and inhibiting motor function recovery. These findings might contribute to the identification of novel therapeutic strategies for SCI.
脊髓损伤（SCI）是一种可导致神经退行性变的创伤性事件。初级运动皮层（M1）中的神经元损伤会阻碍SCI后的运动功能恢复。然而，SCI后神经元损伤的确切机制仍未完全明了。在本研究中，我们发现SCI后M1中的小胶质细胞被激活，这引发了Nod样受体蛋白3（NLRP3）相关的慢性神经炎症和神经元损伤。同时，用小胶质细胞抑制剂米诺环素进行治疗可减少M1中炎症诱导的神经元损伤，保护运动传导通路的完整性，并促进运动功能恢复。此外，我们通过在原代小胶质细胞条件培养基中培养原代神经元来模拟SCI后M1中的慢性炎症，观察到原代神经元也出现了损伤；然而，如观察到的那样，这些效应可通过米诺环素治疗得到缓解。我们的结果表明，M1中的小胶质细胞激活介导了NLRP3相关的神经炎症，并导致M1神经元损伤，从而损害运动传导通路的完整性并抑制运动功能恢复。这些发现可能有助于确定SCI的新型治疗策略。
