Ischemic stroke is a leading cause of death and adult disability worldwide. The redox sensitive transcription factor Nrf2 is a key target for protection in rodent stroke models. We investigated protection afforded by 5 mg/kg dietary sulforaphane in C57BL6/J WT and Nrf2-/- adult male mice subjected to 60min middle cerebral artery occlusion and 72 h or 21 days reperfusion. Behavioural outcomes were measured and brains were sectioned for high throughput imaging and infarct quantification. SFN pretreatment improved functional rotating rod and grip strength performance, significantly reduced cresyl violet infarct volumes and upregulated HO-1 and PPARγ expression in cerebrovascular endothelium. We subsequently conducted the first long-term (>14 day) follow up studies of stroke in Nrf2-deficient and in wild-type mice subjected to long-term pretreatment with SFN (5 mg/kg/day). Basal and inducible contributions of Nrf2 to alternative activation of resident microglia and recruited macrophages, long-term cytokine expression (IL-1β, IL-6, IL-10), post-infarct neurogenesis and angiogenesis and functional recovery were investigated. Our findings highlight the translational potential of Nrf2 inducers in stroke research and establish that dietary levels of sulforaphane afford protection in rodent models of focal cerebral ischaemia.
|Journal||Free Radical Biology and Medicine|
|Volume||108, Supplement 1|
|Early online date||20 Jun 2017|
|Publication status||Published - Jul 2017|