Effect of Myelin Debris on the Phenotypic Transformation of Astrocytes after Spinal Cord Injury in Rats

Abstract

After spinal cord injury (SCI), the accumulation of myelin debris can serve as proinflammatory agents, hindering axon regrowth and exacerbating damage. While astrocytes have been implicated in the phagocytosis of myelin debris, the impact of this process on the phenotypic transformation of astrocytes and their characteristics following SCI in rats is not well understood. Here, we demonstrated that the conditioned medium of myelin debris can trigger apoptosis in rat primary astrocytes in vitro. Using a compressional SCI model in rats, we observed that astrocytes can engulf myelin debris through ATP-binding cassette transporter sub-family A member 1 (ABCA1), and these engulfed cells tend to transform into A1 astrocytes, as indicated by C3 expression. At 4 days post-injury (dpi), astrocytes rapidly transitioned into A1 astrocytes and maintained this phenotype from 4 to 28 dpi, while A2 astrocytes, characterized by S100, were only detected at 14 and 28 dpi. Reactive astrocytes, identified by Nestin, emerged at 4 and 7 dpi, whereas scar-forming astrocytes, marked by N-cadherin, were evident at 14 and 28 dpi. This study illustrates the distribution patterns of astrocyte subtypes and the potential interplay between astrocytes and myelin debris after SCI in rats. We emphasize that myelin debris can induce astrocyte apoptosis in vitro and promote the transformation of astrocytes into A1 astrocytes in vivo. These two classification methods are not mutually exclusive, but rather complementary.

Keywords: astrocyte; myelin debris; phenotypic transformation; rat; spinal cord injury.