P-360 - The dietary isothiocyanate sulforaphane reduces peri-infarct constriction frequency in mouse focal cerebral ischaemia via Nrf2-independent mechanisms

TY - JOUR

T1 - P-360 - The dietary isothiocyanate sulforaphane reduces peri-infarct constriction frequency in mouse focal cerebral ischaemia via Nrf2-independent mechanisms

AU - Farrell-Dillon, Keith

AU - Fraser, Paul

AU - Mann, Giovanni

PY - 2018/5/20

Y1 - 2018/5/20

N2 - Excitotoxic dysfunction exacerbates ischaemic stroke pathology. CNS energy failure leads to ion transport dysregulation and uncontrolled depolarizations, which propagate across the surface of the ischemic cortex as waves. Repolarization taxes energy-deficient tissue, while ion flux drives peri-infarct vascular constrictions (PICs) and mitochondrial free radical production. Sulforaphane (SFN) is a dietary isothiocyanate and inducer of redox defences via the transcription factor Nrf2, previously shown to reduce infarct volume in mice and rats when given i.p. prior to stroke, but its mechanisms of action are still undefined. We quantified peri-infarct constriction waves in mice subjected to 60 min focal cerebral ischemia by laser speckle imaging of the intact skull. Dietary pre-treatment with 5 mg/kg SFN for 3 d reduced PIC incidence in both wild-type (3.66 ±0.21 to 2.00 ±2.00) and Nrf2-/- (4.25 ±0.25 to 1.33 ±0.33) 10-week old male mice, without altering other excitotoxic indices (time to first PIC, propagation speed), n=4–6, p<0.05. Acute administration of 50 mg/kg SFN during ischaemia had no effect on PIC incidence post-administration. These findings highlight an Nrf2-independent protective effect of SFN that results from cumulative dosing at dietary levels.

AB - Excitotoxic dysfunction exacerbates ischaemic stroke pathology. CNS energy failure leads to ion transport dysregulation and uncontrolled depolarizations, which propagate across the surface of the ischemic cortex as waves. Repolarization taxes energy-deficient tissue, while ion flux drives peri-infarct vascular constrictions (PICs) and mitochondrial free radical production. Sulforaphane (SFN) is a dietary isothiocyanate and inducer of redox defences via the transcription factor Nrf2, previously shown to reduce infarct volume in mice and rats when given i.p. prior to stroke, but its mechanisms of action are still undefined. We quantified peri-infarct constriction waves in mice subjected to 60 min focal cerebral ischemia by laser speckle imaging of the intact skull. Dietary pre-treatment with 5 mg/kg SFN for 3 d reduced PIC incidence in both wild-type (3.66 ±0.21 to 2.00 ±2.00) and Nrf2-/- (4.25 ±0.25 to 1.33 ±0.33) 10-week old male mice, without altering other excitotoxic indices (time to first PIC, propagation speed), n=4–6, p<0.05. Acute administration of 50 mg/kg SFN during ischaemia had no effect on PIC incidence post-administration. These findings highlight an Nrf2-independent protective effect of SFN that results from cumulative dosing at dietary levels.

U2 - 10.1016/j.freeradbiomed.2018.04.507

DO - 10.1016/j.freeradbiomed.2018.04.507

M3 - Meeting abstract

SN - 0891-5849

VL - 120, Supplement 1

SP - S154

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -