Electroacupuncture Inhibits Neuroinflammation Induced by Astrocytic Necroptosis Through RIP1/MLKL/TLR4 Pathway in a Mouse Model of Spinal Cord Injury

Astrocytic necroptosis plays an essential role in the progression and regression of neurological disorders, which contributes to the neuroinflammation and disrupts neuronal regeneration and remyelination of severed axons. Electroacupuncture (EA), an effective therapeutic efficacy against spinal cord injury (SCI), has been proved to reduce neuronal cell apoptosis, inhibit inflammation, and prompt neural stem cell proliferation and differentiations. However, there have been few reports on whether EA regulate astrocytic necroptosis in SCI model. To investigate the effects of EA on astrocytic necroptosis and the mechanisms involved in the inhibition of astrocytic necroptosis after SCI in mice by EA, 8-week-old female C57BL/6 mice were subjected to SCI surgery and randomly divided into EA and SCI groups. Mice receiving sham surgery were included as sham group. "Jiaji" was selected as points for EA treatment, 10 min/day for 14 days. The in vitro data revealed that EA treatment significantly improved the nervous function and pathological changes after SCI. EA also reduced the number of GFAP/P-MLKL, GFAP/MLKL, GFAP/HMGB1, and Iba1/HMGB1 co-positive cells and inhibited the expressions of IL-6, IL-1 beta, and IL-33. The results indicate a significant reduction in inflammatory reaction and astrocytic necroptosis in mice with SCI by EA. Additionally, the expressions of RIP1, MLKL, and TLR4, which are associated with necroptosis, were found to be downregulated by EA. In this study, we confirmed that EA can inhibit neuroinflammation by reducing astrocytic necroptosis through downregulation of RIP1/MLKL/TLR4 pathway in mice with SCI.