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Updated: Apr 20, 2026
A Model for Encephalomyosynangiosis Treatment after Middle Cerebral Artery Occlusion-Induced Stroke in Mice
Published on: June 22, 2022
SPP1-mediated microglial synaptic engulfment modulates the glial-vascular unit: Mechanistic insights into
Chenchen Xu1, Xiaoxiao Li2, Rui Zhao2
1Anhui University of Chinese Medicine, Hefei, Anhui 230012, China; Wannan Medical College, Wuhu, Anhui 241002, China; The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China.
Background:
This study aimed to investigate the protective effect of electroacupuncture (EA) on the glial-vascular unit (GVU) in ischemic stroke (IS) by regulating microglial synaptic phagocytosis through secreted phosphoprotein 1 (SPP1).
Methods:
This study involved basic and clinical aspects. Clinically, our research used EA and non-EA groups to investigate the effect of EA on the functional improvement of patients with IS. Basic research involved a mouse model and the following experimental groupings: middle cerebral artery occlusion reperfusion (MCAO/R) NC group, MCAO/R shSpp1 group, MCAO/R EA group, and MCAO/R shSpp1 EA group. In the MCAO/R shSpp1 and MCAO/R shSpp1 EA groups, AAV-shSpp1 was injected stereotactically into the ipsilateral temporoparietal cortex (3 μL per mouse). Thirty days later, a mouse model of MCAO/R was constructed for the four groups, including the MCAO/R NC group, and the MCAO/R EA group. After 24 h, the MCAO/R EA group and the MCAO/R shSpp1 EA group underwent EA treatment for two weeks. Following behavioral tests, Super-Resolution Vascular Imaging, and Laser Speckle Contrast Imaging, brain tissues were collected for immunofluorescence, TUNEL staining, transmission electron microscopy (TEM), Quantitative Real-Time PCR (RT-qPCR) and western blotting analysis.
Results:
Analysis revealed that EA and Spp1 knockdown restored synaptic structure and synaptic protein expression levels, reduced microglial phagocytic events, improved blood-brain barrier integrity, reduced infarct volume, and improved behavioral performance (P<0.5). When EA was combined with Spp1 knockdown, there was no further improvement in any parameter, thus identifying a ceiling effect and suggesting that SPP1 represented the terminal rate-limiting node in the EA protective chain.
Conclusion:
The downregulation of SPP1 replicated the multicellular protective phenotype of EA, establishing SSP1 as a necessary downstream molecule for EA-induced effects and providing a theoretical and experimental basis for the modernization of acupuncture and a multimodal stroke rehabilitation strategy centered on SPP1 that is both interventional and monitorable.
Insights
Electroacupuncture (EA) protects the brain after ischemic stroke by regulating microglial synaptic phagocytosis via secreted phosphoprotein 1 (SPP1). Downregulating SPP1 mimics EA
Area of Science:
- Neuroscience
- Integrative Medicine
- Stroke Research
Background:
- Ischemic stroke (IS) poses a significant health challenge.
- The glial-vascular unit (GVU) is crucial for brain health and is affected in IS.
- Electroacupuncture (EA) shows potential for IS treatment, but its mechanism is unclear.
Purpose of the Study:
- To investigate the protective effects of EA on the GVU in IS.
- To elucidate the role of microglial synaptic phagocytosis and secreted phosphoprotein 1 (SPP1) in EA's mechanism.
- To explore SPP1 as a potential therapeutic target for IS.
Main Methods:
- Clinical study comparing EA and non-EA groups in IS patients.
- Basic research using a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R).
- Experimental groups included MCAO/R with SPP1 knockdown (shSpp1) and EA treatment, analyzed via advanced imaging and molecular techniques.
Main Results:
- EA and SPP1 knockdown improved synaptic structure, reduced microglial phagocytosis, and enhanced blood-brain barrier integrity.
- Both interventions reduced infarct volume and improved behavioral outcomes in MCAO/R mice.
- SPP1 downregulation replicated EA's protective effects, indicating SPP1 as a key downstream mediator.
Conclusions:
- SPP1 is a critical downstream molecule mediating the neuroprotective effects of EA in ischemic stroke.
- Targeting SPP1 offers a potential therapeutic strategy for stroke rehabilitation.
- This study provides a basis for modernizing acupuncture and developing multimodal stroke therapies.
