Spinal cord injury (SCI) is one of the most devastating traumas, and the aberrant proliferation of astrocytes usually causes neurological deficits. However, the mechanism underlying astrocyte over-proliferation after SCI is unclear. Grin2c (glutamate ionotropic receptor type 2c) plays an essential role in cell proliferation. Our bioinformatic analysis indicated that Grin2c and Ca²⁺ transport functions were inhibited in astrocytes after SCI. Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca²⁺/calmodulin-dependent protein kinase 2b (CaMK2b) pathway in vitro. By screening different inflammatory factors, interleukin 1α (IL1α) was further found to inhibit Grin2c/Ca²⁺/CaMK2b and enhance astrocyte proliferation in an oxidative damage model. Blockade of IL1α using neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI. Overall, this study suggests that IL1α promotes astrocyte proliferation by suppressing the Grin2c/Ca²⁺/CaMK2b pathway after SCI, revealing a novel pathological mechanism of astrocyte proliferation, and may provide potential targets for SCI repair.

脊髓损伤（SCI）是最具破坏性的创伤之一，星形胶质细胞的异常增殖通常会导致神经功能缺损。然而，SCI后星形胶质细胞过度增殖的机制尚不清楚。Grin2c（谷氨酸离子型受体 2c 型）在细胞增殖中发挥重要作用。我们的生物信息分析表明，SCI 后星形胶质细胞中的 Grin2c 和 Ca ²⁺转运功能受到抑制。体外抑制 Grin2c 通过抑制 Ca ²⁺ /钙调蛋白依赖性蛋白激酶 2b (CaMK2b) 途径刺激星形胶质细胞增殖。通过筛选不同的炎症因子，进一步发现白细胞介素1α（IL1α）在氧化损伤模型中可抑制Grin2c/Ca ^{2+ /CaMK2b并增强星形胶质细胞增殖。}使用中和抗体阻断 IL1α 会导致 Grin2c 表达增加并抑制 SCI 后星形胶质细胞增殖。总体而言，本研究提示SCI后IL1α通过抑制Grin2c/Ca ^{2+ /CaMK2b通路促进星形胶质细胞增殖，揭示了星形胶质细胞增殖的新病理机制，并可能为SCI修复提供潜在靶点。}