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

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.