Acupuncture waggle needling alleviates spastic movement disorder in post-stroke rats via GLT-1 activation to modulate Glu/GABA-Gln cycle.

Post-stroke spastic movement disorder (PS-SMD) significantly hinder the rehabilitation of stroke survivors, and evidence suggests that acupuncture yields favorable efficacy for this condition. However, the precise mechanisms of acupuncture effects remain elusive. Hence, this study aims to elucidate the potential mechanisms of a classic motion-style acupuncture method, waggle needling, in alleviating PS-SMD via the lens of the Glu/GABA-Gln cycle. Firstly, multiple behavioral assessments including neurologic function scale, muscle tone scale, open field test, balance beam test, and gait analysis, and electrophysiological test were utilized, to investigate acupuncture's effects on middle cerebral artery occlusion (MCAO) rat model with spastic motor impairment. Then, ELISA, Western blotting, RT-qPCR, and immunofluorescence were used to illustrate the expression alterations of the key proteins in the Glu/GABA-Gln cycle. Lastly, pharmacological interventions using GLT-1 inhibitor and agonist were performed to investigate their impacts on acupuncture's effects. We found that acupuncture alleviated neural damage and muscle spasticity, enhanced autonomous locomotion, motor balance and gait symmetry, and alleviated spinal hyperreflexia in PS-SMD rats. These effects were associated with the enhanced expressions of GLT-1, GAD65/67, GS, and VGAT in the ischemic cortical motor area, leading to the restoration of the Glu/GABA balance. Acupuncture-induced effects were partially attenuated by GLT-1 inhibitor, whereas GLT-1 agonist partially recapitulated these effects. Our results demonstrate that acupuncture waggle needling may improve motor behaviors and alleviate spinal hyperreflexia of PS-SMD rats by modulating the Glu/GABA-Gln cycle via GLT-1 to facilitate the restoration of the Glu/GABA equilibrium.