Unraveling the neuroprotective potential of scalp electroacupuncture in ischemic stroke: A key role for electrical stimulation

[Display omitted] •Scalp electroacupuncture (EA) can protect brain tissues by inhibiting neuroinflammation in ischemic stroke.•Electrical stimulation (ES), as an important component of scalp electroacupuncture, can reduce neuroinflammation and protect neurons.•We first used MEA to establish models of ES for rat brain slices and human cerebral organoids in vitro.•We provide new insights into the mechanisms of scalp EA, emphasizing its efficacy in neuroprotection and modulation of neuroinflammation, and suggests that scalp scalp EA’s neuroprotective effects are partly mediated by the ability of ES to suppress neuroinflammation and protect neurons. This study aims to explore the neuroprotective effects of scalp Electroacupuncture (EA) on ischemic stroke, with a specific focus on the role of electrical stimulation (ES). Employing a rat model of middle cerebral artery occlusion (MCAO), we used methods such as Triphenyl tetrazolium chloride staining, micro-CT scanning, Enzyme linked immunosorbent assay (ELISA), and immunofluorescence to assess the impacts of EA. We further conducted RNA-seq analysis and in vitro experiments with organotypic brain slices and cerebral organoids to explore the underlying mechanisms. Our research revealed that EA notably reduced cerebral infarct volume and improved regional cerebral blood flow in rats following MCAO. Micro-CT imaging showed improved vascular integrity in EA-treated groups. Histological analyses, including HE staining, indicated reduced brain tissue damage. ELISA demonstrated a decrease in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, suggesting improved blood–brain barrier function. Immunofluorescence and Western blot analyses revealed that EA treatment significantly inhibited microglial and astrocytic overactivation. RNA-seq analysis of brain tissues highlighted a downregulation of immune pathways and inflammatory responses, confirming the neuroprotective role of EA. This was further corroborated by in vitro experiments using organotypic brain slices and cerebral organoids, which showcased the efficacy of electrical stimulation in reducing neuroinflammation and protecting neuronal cells. The study highlights the potential of scalp EA, particularly its ES component, in treating ischemic stroke. It provides new insights into the mechanisms of EA, emphasizing its efficacy in neuroprotection and modulation of neuroinflammation, and suggests avenues for optimized treatment strategies in stroke therapy.