Modulating the WNK1-SPAK/OSR1-KCC2 Pathway: Acupuncture's Therapeutic Potential in Mitigating Muscle Hypertonia in Ischemic Stroke Rats.

This study investigated the therapeutic effects of acupuncture on post-stroke muscle hypertonia (PSMH) in rats, focusing on the WNK1-SPAK/OSR1-KCC2 pathway to elucidate its underlying mechanisms and support clinical translation. Behavioral, electrophysiological, TTC staining, AChE staining, and transmission electron microscope analyses were used to assess the efficacy of acupuncture. RT-qPCR, Western blot, and immunofluorescence were used to evaluate the expression of the medullary WNK1-SPAK/OSR1-KCC2 pathway. Pharmacological modulation using WNK463 and Gabazine suggested the involvement of WNK kinase activity. Acupuncture reduced neurological deficits and spasticity, enhanced motor recovery, suppressed spinal motor neuron hyperexcitability, and ameliorated neuromuscular dysfunction and muscular structural abnormality. Mechanistically, it downregulated WNK1, SPAK, and OSR1 and increased membrane KCC2 expression in the medulla oblongata. WNK463 partially mimicked acupuncture's effects, while Gabazine partially reversed them. Acupuncture alleviates muscle hypertonia and enhances locomotor recovery in rats with PSMH, potentially by inhibiting the medullary WNK1-SPAK/OSR1 pathway and thereby upregulating KCC2 expression and membrane localization.