Effect of sinusoidal extremely low-frequency electromagnetic stimulation on neurons and glia in a transient stroke model

Ischemic stroke is one of the leading causes of death worldwide. Nowadays, treatment options despite their benefits, have limited use. Therefore, the search for new therapeutic strategies is imperative. Previous studies proved sinusoidal extremely low-frequency electromagnetic stimulation (ELF-EMS) benefits permanent stroke models and endothelial cells. However, the effect on the neuroinflammatory response and reperfusion stroke models remains unclear. To evaluate ELF-EMS (13.5mT/60Hz) effectiveness and possible immunomodulatory response, behavioral tests, neuronal survival, and glial reactivity were assessed in vivo and in vitro. Results showed that ELF-EMS improved neurological outcome, locomotion, habituation, and anxiety in ischemia /reperfusion models. ELF-EMS also increased neuronal survival in the hippocampus with decreased astrocytes and microglia reactivity and IL-1β expression. In vitro, ELF-EMS decreased neuronal loss, microglia reactivity, and the expression inflammatory markers in organotypic hippocampal cultures submitted to oxygen and glucose deprivation, but not in monocultures. Furthermore, in vitro studies showed that ELF-EMS did not affect proliferation but decreased lipopolysaccharide and ATP-induced microglia migration, possibly by targeting subcellular pathways involving the Piezo1 channel, PI3K/Akt pathway, and Src protein. Overall, ELF-EMS had a beneficial effect on ischemia/reperfusion injury models by improving neurological outcome. This is linked to a protective effect of neurons, a decrease in glial reactivity, and a modulatory effect on neuroinflammation for which cell crosstalk is needed. This study presents new insights into the mechanism of action of sinusoidal ELF-EMS and indicates that this treatment has clinical potential as a new treatment against ischemic stroke. Keywords: extremely low-frequency electromagnetic stimulation; ischemic stroke; ischemia/reperfusion injury; microglia migration; neuronal survival; glia activation; neuroinflammation; Piezo1

Author dc:creator

• MOYA GOMEZ, Amanda

Contributors dc:contributor

• Bronckaers, Annelies
• Pérez Font, Lena
• Brône, Bert

Statement dc:rights

• info:eu-repo/semantics/embargoedAccess

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/1942/42334

OAI identifier oai:identifier

oai:documentserver.uhasselt.be:1942/42334