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Acupuncture Modulates NMDAR-PP1/Calpain1-KCC2 Pathway to Ameliorate Spinal Hyperexcitability and Spastic Hemiplegia Induced by Ischemic Stroke.

Journal of integrative neuroscienceยทDecember 2025ยทJia-Ling He, Liang-Xiao Ma, Yu-Xin Zhuang et al.
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Key Finding

Acupuncture significantly reduced post-stroke spastic hemiplegia by modulating the NMDAR-PP1/Calpain1-KCC2 pathway in spinal cord, thereby suppressing neuronal hyperexcitability and improving motor function in MCAO rats.

What This Means For You

Researchers investigated how acupuncture helps reduce muscle spasticity and improve movement after stroke. Many stroke survivors experience spastic hemiplegia, a condition causing stiff, tight muscles on one side of the body that makes movement difficult. This happens partly because the spinal cord becomes overexcited after a stroke damages the brain's ability to properly regulate it.

In this study, scientists used rats with induced strokes to test acupuncture's effects. They measured muscle tone, walking patterns, nerve activity in the spinal cord, and examined various proteins and cellular pathways involved in nerve signaling. The researchers found that acupuncture significantly reduced muscle stiffness and improved the rats' ability to walk and move normally.

The study revealed how acupuncture works at a molecular level. After stroke, certain proteins in the spinal cord become imbalanced, leading to overactive nerve cells that cause spasticity. Acupuncture helped restore this balance by influencing a specific pathway involving NMDA receptors and a protein called KCC2. By modulating these proteins, acupuncture reduced the hyperexcitability of spinal cord neurons, which directly decreased muscle spasticity.

These findings suggest acupuncture may be a valuable treatment option for stroke survivors struggling with spasticity. The research provides scientific evidence for acupuncture's mechanism of action at the cellular level, which could help integrate it more fully into conventional stroke rehabilitation programs. While this study was conducted in animals, it offers promising insights that may translate to human treatment. Patients interested in acupuncture for post-stroke spasticity should consult with a licensed acupuncturist experienced in neurological rehabilitation.

Clinical Notes for Practitioners

This study examined acupuncture's effects on post-stroke spastic hemiplegia (PSSH) using male rats with middle cerebral artery occlusion (MCAO). Researchers employed multiple assessment methods including neurological function scores, muscle tone scales, footprint analysis, H-reflex recordings, c-Fos immunofluorescence, RT-qPCR, and Western blot analysis. Results demonstrated that acupuncture significantly reduced spasticity, improved motor performance, and decreased spinal ventral horn hyperexcitability. Mechanistically, acupuncture downregulated NMDAR1 expression and restored KCC2 expression and function in the spinal cord. Pharmacological interventions with NMDAR agonists and antagonists confirmed that acupuncture upregulates KCC2 by inhibiting NMDAR-mediated activation of PP1 and Calpain1 pathways. The study provides evidence that acupuncture modulates the NMDAR-PP1/Calpain1-KCC2 pathway to suppress neuronal hyperexcitability in spinal cord, offering mechanistic insight into acupuncture's therapeutic effects on spasticity. Clinical takeaway: Acupuncture represents a scientifically supported intervention for PSSH that directly addresses spinal hyperexcitability through specific molecular pathways.

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