Early Intervention with Electrical Stimulation Reduces Neural Damage After Stroke in Non-human Primates

Abstract

Ischemic stroke is a neurological condition that results in significant mortality and long-term disability for adults, creating huge health burdens worldwide. For stroke patients, acute intervention offers the most critical therapeutic opportunity as it can reduce irreversible tissue injury and improve functional outcomes. However, currently available treatments within the acute window are highly limited. Although emerging neuromodulation therapies have been tested for chronic stroke patients, acute stimulation is rarely studied due to the risk of causing adverse effects related to ischemia-induced electrical instability. To address this gap, we combined electrophysiology and histology tools to investigate the effects of acute electrical stimulation on ischemic neural damage in non-human primates. Specifically, we induced photothrombotic lesions in the monkey sensorimotor cortex while collecting electrocorticography (ECoG) signals through a customized neural interface. Gamma activity in ECoG was used as an electrophysiological marker to track the effects of stimulation on neural activation. Meanwhile, histological analysis including Nissl, cFos, and microglial staining was performed to evaluate the tissue response to ischemic injury. Comparing stimulated monkeys to controls, we found that theta-burst stimulation administered directly adjacent to the ischemic infarct at 1 hour post-stroke briefly inhibits peri-infarct neuronal activation as reflected by decreased ECoG gamma power and cFos expression. Meanwhile, lower microglial activation and smaller lesion volumes were observed in animals receiving post-stroke stimulation. Together, these results suggest that acute electrical stimulation can be used safely and effectively as an early stroke intervention to reduce excitotoxicity and inflammation, thus mitigating neural damage and enhancing stroke outcomes.