Acupuncture Activates PI3K/Akt Pathway to Promote Spinal Microglial M2 Polarization and Alleviate Spastic Hemiplegia Following Ischemic Stroke

Purpose: Studies showed that post-ischemic spastic hemiplegia can be linked to neuroinflammation mediated by microglial polarization. Microglial M1/M2 polarization is regulated by the PI3K/Akt pathway. We previously reported that acupuncture alleviated spasticity after permanent middle cerebral artery occlusion (p-MCAO). This study investigated whether its antispastic effects were associated with activation of the spinal PI3K/Akt pathway and promotion of microglial M2 polarization.

Methods: p-MCAO was induced in Sprague-Dawley rats to establish a model of spastic hemiplegia. Yanglingquan (GB34) was needled using waggle needling, a motion‑style acupuncture technique. Its association with spasticity alleviation and motor recovery was evaluated by behavioral assessments, TTC staining, and the H-reflex test. Molecular analyses were performed to investigate the underlying mechanisms. Minocycline was used to examine the role of microglial polarization, while LY294002 and 740Y-P were used to determine whether the effects of acupuncture were mediated through the PI3K/Akt pathway.

Results: Rats with p-MCAO-induced spastic hemiplegia exhibited neurological deficits, increased muscle tone, motor dysfunction, and spinal hyperexcitability, together with microglial M1 polarization, inflammatory responses, spinal excitatory/inhibitory imbalance, and suppressed PI3K/Akt activity. Acupuncture at GB34 alleviated spasticity and promoted motor recovery. It also activated the spinal PI3K/Akt pathway, promoted microglial M2 polarization, reduced IL-6 and TNF-α, and increased IL-10 and TGF-β. In addition, acupuncture attenuated spinal hyperexcitability, as indicated by improvement in the H-reflex, and restored spinal excitatory/inhibitory balance, as reflected by regulation of vGluT1/vGAT-associated synaptic markers and Glu/GABA levels. Minocycline produced partially similar improvements, whereas LY294002 partially blocked the effects of acupuncture and 740Y-P only partially mimicked them.

Conclusion: Acupuncture alleviates spastic hemiplegia by activating the PI3K/Akt pathway and promoting spinal microglial M2 polarization. These findings support its potential clinical application for post-stroke spasticity and identify the PI3K/Akt pathway as a potential therapeutic target.