Electroacupuncture ameliorates cognitive impairment after spinal cord injury via BDNF/TrkB/CREB-mediated hippocampal neurorestoration.

BACKGROUND

Spinal cord injury (SCI) induces severe cognitive impairment that significantly impedes post-injury rehabilitation. Hippocampal synaptic dysfunction and myelin damage constitute key underlying pathogenic mechanisms of cognitive decline. While electroacupuncture (EA) has demonstrated promise in ameliorating cognitive deficits and promoting neurological recovery after SCI, whether it can rescue SCI-associated cognitive impairment and its mechanistic basis remains incompletely understood.

METHODS

SCI was induced in rats using the modified Allen's weight-drop technique. EA-treated rats received daily 20-min stimulation at Dazhui (GV14) and Mingmen (GV4) acupoints with sterilized stainless-steel needles. Hindlimb motor function was assessed by Basso-Beattie-Bresnahan (BBB) scoring and inclined plane testing; cognitive performance via Y-maze and novel object recognition (NOR). Neuronal morphology was analyzed by hematoxylin-eosin (HE) staining and transmission electron microscope (TEM). Synaptic plasticity and myelin integrity were evaluated using immunofluorescence (IF) and TEM. ELISA quantified BDNF levels in serum, spinal cord, and hippocampus; Western blotting assessed the protein expression of key synaptic structural proteins (PSD95 and SYN), alongside BDNF, TrkB, and CREB.

RESULTS

EA markedly improved hindlimb motor function and ameliorated cognitive deficits in SCI rats. EA treatment restored hippocampal cytoarchitecture, repaired synaptic ultrastructure, and preserved myelin integrity versus sham group. Concomitant upregulation of synaptic plasticity markers and myelin-related proteins was observed. Significantly, EA elevated BDNF levels in serum, spinal cord, and hippocampus, and activated the hippocampal BDNF/TrkB/CREB pathway.

CONCLUSION

These findings demonstrate that electroacupuncture (EA) not only enhances motor recovery in spinal cord injury but also effectively mitigates post-SCI cognitive impairment and restores hippocampal neuronal morphology. This therapeutic effect is mediated through EA-induced activation of the BDNF/TrkB/CREB pathway, which which drives the synthesis of synaptic structural proteins, attenuates synaptic dysfunction and ameliorates myelin damage in hippocampal neurons.