SPP1-mediated microglial synaptic engulfment modulates the glial-vascular unit: Mechanistic insights into electroacupuncture for ischemic stroke.

Researchers investigated how electroacupuncture (EA) protects the brain after ischemic stroke by examining its effects on blood vessels, brain cells, and connections between neurons. The study included both stroke patients and laboratory mice. In the clinical portion, stroke patients receiving electroacupuncture showed improved functional recovery compared to those who didn't receive it. In the laboratory study, scientists discovered that electroacupuncture works by controlling a protein called SPP1, which regulates how immune cells in the brain (microglia) clean up damaged neural connections after a stroke. When researchers used electroacupuncture on mice after inducing stroke, they found it restored the structure of neural connections, reduced brain damage, improved blood-brain barrier integrity, decreased the volume of damaged tissue, and enhanced behavioral recovery. Interestingly, when they blocked SPP1 protein production, it produced the same protective effects as electroacupuncture, and combining both treatments didn't provide additional benefits. This suggests SPP1 is the key mechanism through which electroacupuncture provides its protective effects. The findings are significant because they explain how electroacupuncture works at the molecular level to protect multiple types of brain cells after stroke. This research provides scientific evidence supporting electroacupuncture as part of stroke rehabilitation and identifies SPP1 as a potential target for monitoring treatment effectiveness. If you're considering electroacupuncture for stroke recovery, consult with a licensed acupuncturist experienced in neurological rehabilitation.

This translational study examined electroacupuncture's neuroprotective mechanisms in ischemic stroke through SPP1-mediated microglial synaptic phagocytosis regulation. Clinical results demonstrated functional improvement in EA-treated stroke patients versus controls. The murine MCAO/R model (n=4 groups) compared EA treatment, Spp1 knockdown via AAV-shSpp1 stereotactic injection, and combined interventions over two weeks post-stroke. Both EA and Spp1 knockdown independently restored synaptic architecture and protein expression, reduced microglial phagocytic activity, improved blood-brain barrier integrity, decreased infarct volume, and enhanced behavioral outcomes (P<0.05). Critically, combining EA with Spp1 knockdown produced no additive benefits, establishing a ceiling effect. This identifies SPP1 as the terminal rate-limiting node in EA's protective cascade. Immunofluorescence, TEM, RT-qPCR, Western blot, super-resolution vascular imaging, and laser speckle contrast imaging confirmed multicellular protective effects. Clinical implication: SPP1 represents a quantifiable biomarker for EA efficacy in stroke rehabilitation and a potential multimodal therapeutic target.