Inflammatory Factor IL1α Induces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca(2+)/CaMK2b Pathway

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 Ca(2+) transport functions were inhibited in astrocytes after SCI.

Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca(2+)/calmodulin-dependent protein kinase 2b (CaMK2b) pathway in vitro.

By screening different inflammatory factors, interleukin 1α (IL1α) was further found to inhibit Grin2c/Ca(2+)/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/Ca(2+)/CaMK2b pathway after SCI, revealing a novel pathological mechanism of astrocyte proliferation, and may provide potential targets for SCI repair.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-023-01128-4.