engleski

Hyperbaric oxygenation and 20- hydroxyeicosatetreanoic acid inhibition reduce stroke volume in female diabetic Sprague–Dawley rats

We evaluated the effects of acute and repetitive hyperbaric oxygenation (HBO2), 20- HETE inhibition by N-hydroxy-N'-(4-butyl- 2methylphenyl)-formamidine (HET0016) and their combinations on experimental stroke outcomes. Streptozotocin-induced type-1 diabetic Sprague- Dawley female rats (N=42, N=7/group), were subjected to 30’ transient middle cerebral artery occlusion (t-MCAO) / reperfusion and divided in following groups ; a) Control group, without treatment ; and groups exposed to: b) HBO2 ; c) multiple HBO2 (HBO2 immediately and second exposure 12h after t-MCAO) ; d) HET0016 pretreatment (1mg/kg/3 days prior to t-MCAO) combined with HBO2 after t-MCAO ; e) HET0016 treatment (1h before, during and for 6 hours after t-MCAO) ; and f) HET0016 treatment followed by HBO2 after t-MCAO. mRNA expression of CYP2J3, CYP2C11, CYP4A1, eNOS and EPHX2 was determined by real-time qPCR. Cortical infarct size and total infarct size were equally significantly reduced in HBO2 and HET0016 treated rats. Combined treatment with HET0016 and HBO2 provided no significant additive effect compared to HET0016 treatment only. mRNA of Cyp2J3 was significantly increased in all study groups, and mRNA of Cyp2C11 was significantly increased in multiple HBO2 and HET0016 treatment followed by HBO2 groups, compared to Control. eNOS expression was significantly increased after HBO2 treatments and expression of EPHX2 was increased in all groups compared to Control group. In diabetic female SD rats HBO2 and HET0016 are highly effective stroke treatments, suggesting involvement of CYP450 metabolites and NO pathway in this therapeutic effect.

Brain ischemia ; stroke ; hyperbaric oxygenation ; diabetes mellitus

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