Continual Deletion of Spinal Microglia Reforms Astrocyte Scar Favoring Axonal Regeneration

脊髓小胶质细胞的持续清除可重塑星形胶质细胞瘢痕,从而促进轴突再生。

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作者:Longkuo Xia ,Jianhuan Qi ,Mingming Tang ,Jing Liu ,Da Zhang ,Yanbing Zhu ,Baoyang Hu

Abstract

Astrocyte scar formation after spinal cord injury (SCI) efficiently limits the accurate damage but physically restricts the following axon regeneration. Lately, fine tuning scar formation is becoming a novel strategy to develop SCI treatment, yet how to leverage these opposite effects remains challenging. Here, utilizing an improved drug administration approach, we show that in a mouse model of spinal cord injury, continual deletion of microglia, especially upon scar formation, by pexidartinib decreases the amount of microglia-derived collagen I and reforms the astrocyte scar. The astrocytes become less compacted in the scar, which permits axon regeneration and extension. Although continual microglia deletion did not significantly improve the locomotive performance of the SCI mice, it did ameliorate their weight loss, possibly by improving their relevant health conditions. We thus identified a novel approach to regulate astrocyte scars for improved axon regeneration, which is indicative of the clinical treatment of SCI patients.

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