YO-05 - Long-term contribution of Nrf2 to behavioral recovery following focal cerebral ischemia-reperfusion injury: Abstracts of the OCC World Congress and Annual SFRR-E Conference 2017 Metabolic Stress and Redox Regulation Berlin, Germany 21-23 June 2017

TY - JOUR

T1 - YO-05 - Long-term contribution of Nrf2 to behavioral recovery following focal cerebral ischemia-reperfusion injury

T2 - Abstracts of the OCC World Congress and Annual SFRR-E Conference 2017 Metabolic Stress and Redox Regulation Berlin, Germany 21-23 June 2017

AU - Farrell-Dillon, Keith

AU - Chapple, Sarah

AU - Fraser, Paul

AU - Mann, Giovanni

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

KW - Nrf2

KW - Stroke

KW - M2

KW - Ischaemia

U2 - 10.1016/j.freeradbiomed.2017.04.079

DO - 10.1016/j.freeradbiomed.2017.04.079

M3 - Meeting abstract

SN - 0891-5849

VL - 108, Supplement 1

SP - S16

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -