Microglial activation in the motor cortex mediated NLRP3-related neuroinflammation and neuronal damage following spinal cord injury

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 in vivo. 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 in vitro; however, as observed in vivo, 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.