Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice

Despite progress in reperfusion therapy, functional recovery remains suboptimal in many stroke patients, with oxidative stress, inflammation, dysbiosis, and secondary neurodegeneration constituting the major hurdles to recovery. The essential trace element selenium is emerging as a promising therapeutic agent for stroke. However, although several rodent studies have shown that selenium can protect against cell loss following cerebral ischemia, no study has yet examined whether selenium can enhance long-term functional recovery. Moreover, published studies have typically reported a single mechanism of action underlying selenium-mediated stroke recovery. However, we propose that selenium is more likely to have multifaceted actions. Here, we show that selenomethionine confers a potent neuroprotective effect in a canonical filament-induced transient middle cerebral artery occlusion (tMCAO) mouse model. Post-tMCAO selenium treatment significantly reduces the cerebral infarct volume, oxidative stress, and ferroptosis and enhances post-tMCAO motor performance in the acute phase after stroke. Moreover, analysis of the gut microbiota reveals that acute selenium treatment reverses stroke-induced gut dysbiosis. Longer-term selenium supplementation activates intrinsic neuroprotective mechanisms, prevents secondary neurodegeneration, alleviates systemic inflammation, and diminishes gut microbe-derived circulating trimethylamine N-oxide. These findings demonstrate that selenium treatment even after cerebral ischemia has long-term and multifaceted neuroprotective effects, highlighting its clinical potential.

Automated summary

Despite progress in reperfusion therapy, functional recovery after stroke remains suboptimal. Selenium is emerging as a promising therapeutic agent for stroke, but its long-term effects and mechanisms of action are not well understood. This study demonstrates that selenium treatment in a mouse model of stroke has long-term neuroprotective effects and reduces cerebral infarction, oxidative stress, and ferroptosis. Selenium supplementation also improves motor performance and reverses stroke-induced gut dysbiosis. These findings highlight the multifaceted and clinical potential of selenium in stroke treatment.