Electric muscle stimulation attenuates neuroinflammation and improves the outcome of acute ischemic stroke in mice

Törteli, Anna and Kozák, Péter and Uno, Hiroyuki and Hősi, Rajmund and Ruppert, Zsófia and Gáspár, Eszter and Bari, Ferenc and Török, Zsolt and Farkas, Eszter and Tóth, Erzsébet Melinda and Menyhárt, Ákos (2026) Electric muscle stimulation attenuates neuroinflammation and improves the outcome of acute ischemic stroke in mice. NEUROTHERAPEUTICS, 23 (4). No. e00933. ISSN 1933-7213

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Abstract

Acute ischemic stroke is a major cause of death and disability, yet many patients cannot engage in early rehabilitation due to severe motor deficits. Resulting immobility accelerates muscle atrophy and systemic inflammation, highlighting muscle–brain interactions as potential therapeutic targets. Electrical muscle stimulation (EMS) provides a non-volitional means of activating skeletal muscle and may mimic key neuroprotective features of exercise. We tested whether hyperacute EMS modulates muscle-to-brain signaling to improve stroke outcomes. Transient middle cerebral artery occlusion was induced in male and female C57BL/6 mice, followed by daily neurological assessments and 4 Hz lower-limb EMS for three days. Myofiber morphology, infarct size, blood lactate, and muscle and brain gene expression were subsequently analyzed. EMS preserved myofiber size and reduced stress-response gene expression (Hsp25, Hspb8, Atf4) in skeletal muscle. In the brain, EMS decreased infarct volume, limited necrosis, and improved neurological function. Stroke-associated inflammation was attenuated, evidenced by reduced Tnf, Nlrp3 and Aif1 expression. EMS elevated circulating lactate, while stroke groups showed increased expression of the monocarboxylate transporter Mct-1, supporting a lactate-dependent metabolic coupling mechanism. These findings identify hyperacute EMS as a feasible, noninvasive intervention that confers neuroprotective and anti-inflammatory benefits after stroke, potentially via lactate-mediated muscle-to-brain signaling. EMS may represent a valuable adjunct for patients unable to mobilize during the critical early phase of stroke recovery. © 2026 The Author(s). Published by Elsevier Inc. on behalf of American Society for Experimental NeuroTherapeutics. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

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