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This study aimed to examine whether electroacupuncture (EA) could improve CBF following an acute ischemic injury by regulating leptomeningeal collaterals. The clinical outcomes suggest that EA resulted in an increase in the average CBF within the whole brain and gray matter of healthy subjects compared to pre-intervention. The experiments conducted on animals revealed that EA was able to improve neurological function, reduce infarct volume, and salvage tissue damage in the peri-infarct areas of permanent middle cerebral artery occlusion rats. Additionally, EA was found to increase cerebral perfusion and the diameter of developed leptomeningeal anastomoses, accompanied by activation of cholinergic neurons of the nucleus basalis of Meynert (NBM). However, these effects of EA were reversed by chemogenetic inhibition of cholinergic neurons in the NBM or by intraperitoneal injection of acetylcholine receptors antagonist atropine. These findings suggest that EA improved CBF after acute ischemic stroke, partially via activating cholinergic projections from the NBM to the cortex, thereby promoting leptomeningeal collateral circulation. 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