GDF11 alleviates spinal cord injury in rats by modulating microglia polarization through Smad2/3 and MAPK/NFκB signaling pathways.

BACKGROUND

Inflammatory response after spinal cord injury is an important factor in further exacerbating the extent of spinal cord injury. The polarization of microglia plays a pivotal role in the inflammatory cascade after SCI. This study investigated whether exogenous Growth Differentiation Factor 11 (GDF11) mitigates neuroinflammation and improves functional recovery by modulating M1/M2 microglial polarization, exploring its therapeutic potential for SCI.

METHODS

The protective and anti-inflammatory effect of GDF11 on LPS-induced microglia polarization was examined in vitro study. An Allen model of spinal cord injury was established to detect the therapeutic effects of GDF11. Transcriptome sequencing elucidated GDF11's downstream pathways.

RESULTS

GDF11 effectively improved histological and functional recovery in SCI rats. In vitro studies we found that GDF11 improved LPS-mediated M1 polarization state of microglia and was able to promote the conversion of M1 macrophages to M2 macrophages. The anti-inflammatory effects of GDF11 were associated with the activation of the TGF-β signaling pathway and the inhibition of MAPK and NF-κB activation.

CONCLUSION

The present study reveals that GDF11 alleviates secondary injury after SCI by reprogramming microglial polarization, highlighting its promise as a novel therapeutic target.