Exercise therapy facilitates neural remodeling and functional recovery post-spinal cord injury via PKA/CREB signaling pathway modulation in rats

Neuronal structure is disrupted after spinal cord injury (SCI), causing functional impairment. The effectiveness of exercise therapy (ET) in clinical settings for nerve remodeling post-SCI and its underlying mechanisms remain unclear. This study aims to explore the effects and related mechanisms of ET on nerve remodeling in SCI rats.

We randomly assigned rats to various groups: sham-operated group, sham-operated + ET, SCI alone, SCI + H89, SCI + ET, and SCI + ET + H89. Techniques including motor-evoked potential (MEP), video capture and analysis, the Basso–Beattie–Bresnahan (BBB) scale, western blotting, transmission electron microscopy, hematoxylin and eosin staining, Nissl staining, glycine silver staining, immunofluorescence, and Golgi staining were utilized to assess signal conduction capabilities, neurological deficits, hindlimb performance, protein expression levels, neuron ultrastructure, and tissue morphology. H89—an inhibitor that targets the protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway—was employed to investigate molecular mechanisms.

This study found that ET can reduce neuronal damage in rats with SCI, protect residual tissue, promote the remodeling of motor neurons, neurofilaments, dendrites/axons, synapses, and myelin sheaths, reorganize neural circuits, and promote motor function recovery. In terms of mechanism, ET mainly works by mediating the PKA/CREB signaling pathway in neurons.

Our findings indicated that: (1) ET counteracted the H89-induced suppression of the PKA/CREB signaling pathway following SCI; (2) ET significantly alleviated neuronal injury and improved motor dysfunction; (3) ET facilitated neuronal regeneration by mediating the PKA/CREB signaling pathway; (4) ET enhanced synaptic and dendritic spine plasticity, as well as myelin sheath remodeling, post-SCI through the PKA/CREB signaling pathway.