Activin A enhances neurofunctional recovery following traumatic spinal cord injury by inhibiting autophagy

This is the authors' abstract. We don't add key points for this paper.

JOURNAL/nrgr/04.03/01300535-202606000-00063/figure1/v/2026-02-11T151048Z/r/image-tiff In the early stages of traumatic spinal cord injury, extensive accumulation of autophagosomes creates a neurotoxic microenvironment, exacerbating neuronal cell death and worsening tissue damage, ultimately hindering neurofunctional recovery. Activin A is a critical growth factor necessary for the development of the embryonic nervous system and for maintaining neuronal function in the adult cerebral cortex. It can inhibit excessive autophagy in ischemic stroke to reduce neuronal damage. However, the specific mechanism through which Activin A functions in the spinal cord remains poorly understood. In this study, we administered different concentrations of Activin A to neural stem cells from the spinal cord and found that Activin A stimulated the proliferation and neuronal differentiation of neural stem cells. Then, we established an in vitro oxidative stress model by using hydrogen peroxide to stimulate the neural stem cells-induced neurons. We found that Activin A could reduce apoptosis caused by oxidative stress. Subsequently, we treated a mouse model of spinal cord contusion with intrathecal injection of Activin A. Behavioral and electrophysiological results showed that Activin A promoted recovery of motor function and reconstruction of neural circuits in the model mice. Finally, RNA sequencing indicated that Activin A inhibited autophagy by activating the PI3K/AKT/mTOR pathway and upregulating the expression of synaptogenesis-related factor Sema3A in the spinal cord. These results suggest that Activin A may mediate the excessive autophagic response after spinal cord injury, promote the reconstruction of damaged neural circuits, and restore neurological function in the injured spinal cord.