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• W2159382021 abstract "Stilbazulenyl nitrone (STAZN) is a potent lipophilic second-generation azulenyl nitrone antioxidant, which is highly neuroprotective in rodent models of cerebral ischemia and trauma. This study was conducted to establish whether the neuroprotection induced by STAZN persists with chronic survival and to characterize STAZN′s pharmacokinetics. Physiologically regulated rats received a 2-h middle cerebral artery occlusion by intraluminal suture and were treated with either STAZN [four 0.6 mg/kg doses i.p. administered at 2 (i.e., onset of recirculation), 4, 24, and 48 h; <i>n</i> = 16] or dimethyl sulfoxide vehicle (<i>n</i> = 11). They received sequential neurobehavioral examinations followed by quantitative neuropathology at 30 days. STAZN improved neurological deficits compared with vehicle controls, beginning within <2 h of the first dose and persisting throughout a 30-day survival. Large cystic necrotic infarcts were common in vehicle-treated rats but infrequent in STAZN-treated rats, and noninfarcted forebrain tissue was increased on average by 15%. In normal rats administered 5 mg/kg STAZN i.v. in Solutol HS 15/ethanol/saline vehicle, STAZN blood levels exhibited a biexponential decline, with an initial half-life of 28 min and a subsequent slow decay with half-life of ∼7 h. STAZN tissue levels at 2 to 3 h were, on average, 2.5% of blood levels in forebrain, 56% in myocardium, and 41% in kidney. STAZN was concentrated in liver with initial concentrations averaging 5.2-fold above blood levels and a subsequent linear decline of 40% between 24 and 72 h. These results establish that STAZN confers enduring ischemic neuroprotection, has a long circulating half-life, and penetrates well into brain and other organs—characteristics favoring its potential therapeutic utility." @default.
• W2159382021 created "2016-06-24" @default.
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• W2159382021 date "2005-02-16" @default.
• W2159382021 modified "2023-09-23" @default.
• W2159382021 title "Stilbazulenyl Nitrone, a Second-Generation Azulenyl Nitrone Antioxidant, Confers Enduring Neuroprotection in Experimental Focal Cerebral Ischemia in the Rat: Neurobehavior, Histopathology, and Pharmacokinetics" @default.
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• W2159382021 doi "https://doi.org/10.1124/jpet.105.083386" @default.
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