biostudies-literatureJia JIntramural NIH HHSNHLBI NIH HHSNINDS NIH HHSNIGMS NIH HHS75-85https://www.ebi.ac.uk/biostudies/studies/S-EPMC4834246biostudies-literatureUnknown279<h4>Objective</h4>Cytochrome P450 epoxygenases (CYP) metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), which exhibit vasodilatory, anti-inflammatory and neuroprotective actions in experimental cerebral ischemia. We evaluated the effect of endothelial-specific CYP overexpression on cerebral blood flow, inflammatory cytokine expression and tissue infarction after focal cerebral ischemia in transgenic mice.<h4>Approach and results</h4>Male and female wild-type and transgenic mice overexpressing either human CYP2J2 or CYP2C8 epoxygenases in vascular endothelium under control of the Tie2 promoter (Tie2-CYP2J2 and Tie2-CYP2C8) were subjected to 60-min middle cerebral artery occlusion (MCAO). Microvascular cortical perfusion was monitored during vascular occlusion and reperfusion uExperimental neurologySex- and isoform-specific mechanism of neuroprotection by transgenic expression of P450 epoxygenase in vascular endothelium.PMC4834246R01GM088199P01 NS049210R01 HL093140R01 GM088199R01 NS044313P01NS049210R01 NS070837R01HL093140Z01 ES025034R01NS070837DeGraff LMDavis CMGraves JPLee CRJia JZhang WZeldin DCAlkayed NJJia TWang REdin MLJouihan SRonnekleiv OBradbury JAXu YfalseSex- and isoform-specific mechanism of neuroprotection by transgenic expression of P450 epoxygenase in vascular endothelium.<h4>Objective</h4>Cytochrome P450 epoxygenases (CYP) metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), which exhibit vasodilatory, anti-inflammatory and neuroprotective actions in experimental cerebral ischemia. We evaluated the effect of endothelial-specific CYP overexpression on cerebral blood flow, inflammatory cytokine expression and tissue infarction after focal cerebral ischemia in transgenic mice.<h4>Approach and results</h4>Male and female wild-type and transgenic mice overexpressing either human CYP2J2 or CYP2C8 epoxygenases in vascular endothelium under control of the Tie2 promoter (Tie2-CYP2J2 and Tie2-CYP2C8) were subjected to 60-min middle cerebral artery occlusion (MCAO). Microvascular cortical perfusion was monitored during vascular occlusion and reperfusion u2016-01-01T00:00:00Z2016 May2025-04-04T08:49:47.971Z2019-06-06T15:43:00ZS-EPMC48342462690247310.1016/j.expneurol.2016.02.016