Effect of electroacupuncture on vascular remodeling in rats with cerebral ischemia by regulating irisin based on VEGF/Akt/eNOS signaling pathway

Lu Cao; Wenchao Ding; Yashuo Feng; Chong Guan; Li Liu; Hongyu Xie; Kewei Yu; Dongyan Xu; Lijuan Zhao; Xuan Sha; Xiaoman Deng; Santian Wu; Yangrui Wang; Yi Wu; Tingting Zhang; Nianhong Wang

doi:10.1016/j.brainresbull.2025.111192

Effect of electroacupuncture on vascular remodeling in rats with cerebral ischemia by regulating irisin based on VEGF/Akt/eNOS signaling pathway

Brain Res Bull. 2025 Jan 9:111192. doi: 10.1016/j.brainresbull.2025.111192. Online ahead of print.

Authors

Lu Cao¹, Wenchao Ding², Yashuo Feng³, Chong Guan³, Li Liu⁴, Hongyu Xie⁴, Kewei Yu⁴, Dongyan Xu⁴, Lijuan Zhao³, Xuan Sha³, Xiaoman Deng³, Santian Wu³, Yangrui Wang⁵, Yi Wu⁶, Tingting Zhang⁷, Nianhong Wang⁸

Affiliations

¹ School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Geriatric Diseases, Huashan Hospital, Fudan University, Shanghai, China; Institute of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Department of Orthopaedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.
⁴ Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.
⁵ Living Word Shanghai, Shanghai, China.
⁶ Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Geriatric Diseases, Huashan Hospital, Fudan University, Shanghai, China.
⁷ School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: [email protected].
⁸ School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Geriatric Diseases, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: [email protected].

PMID: 39798935
DOI: 10.1016/j.brainresbull.2025.111192

Abstract

Objective: This study aimed to explore the cumulative effects and expression patterns of electroacupuncture (EA) on irisin secretion, observe the effects of EA on the recovery of neurobehavioral function and vascular remodeling after cerebral ischemia, and elucidate the mechanism by which EA promotes vascular remodeling by regulating irisin expression.

Methods: A rat model of left middle cerebral artery occlusion (MCAO) was prepared, and EA was performed. Tissue distribution and expression of irisin were determined by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Type III fibronectin domain protein 5-silenced adeno-associated virus (rAAV-shFNDC5) was injected into the lateral ventricle as a control. Neurobehavioral function was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and behavioral experiments, while vascular remodeling was evaluated using laser speckle blood flow imaging, and the expressions of irisin and vascular remodeling-related factors were measured by ELISA and Western blotting.

Results: The number of FNDC5-positive neurons, fluorescence intensity, and irisin expression reached their maximum increase after 7 days of EA treatment. In addition, the EA group exhibited a significant reduction in cerebral infarct volume and impairment of neurobehavioral function, an increase in cerebral blood flow and microvascular diameter on the ischemic side, and significantly higher expression levels of FNDC5, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS). However, rAAV-shFNDC5 significantly weakened the therapeutic effects of EA.

Conclusions: EA upregulated irisin expression, reaching a peak after 7 days of EA and then stabilizing. EA facilitated vascular remodeling after cerebral ischemia, and this might be associated with the activation of the irisin-mediated VEGF/Akt/eNOS signaling pathway.

Keywords: Electroacupuncture; Irisin; Ischemic stroke; Vascular remodeling.