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首页> 外文期刊>Neurochemical Research >Delayed Treatment with Carboxy-PTIO Permits a 4-h Therapeutic Window of Opportunity and Prevents Against Ischemia-Induced Energy Depletion Following Permanent Focal Cerebral Ischemia in Mice
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Delayed Treatment with Carboxy-PTIO Permits a 4-h Therapeutic Window of Opportunity and Prevents Against Ischemia-Induced Energy Depletion Following Permanent Focal Cerebral Ischemia in Mice

机译:羧基-PTIO的延迟治疗允许4小时治疗性机会窗并预防小鼠局灶性局灶性脑缺血后缺血引起的能量消耗

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摘要

We examined whether a nitric oxide scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-l-oxyl-3-oxide (carboxy-PTIO), could offer neuroprotective actions and improve cerebral energy metabolism in a model of stroke. Sixty C57BL/10J mice were given either carboxy-PTIO (0.3–1.2 mg/kg) or vehicle intraperitoneally, 0.5 h after permanent middle cerebral artery occlusion, to evaluate the dose–response effects. An additional 70 animals received carboxy-PTIO (0.6 mg/kg) or vehicle, 2–6 h post-ischemia, for establishing the therapeutic window. Subgroups of animals, treated with carboxy-PTIO (0.6 mg/kg) or vehicle, were used for measuring cerebral bioenergetic metabolites (ATP, ADP, AMP, adenosine). Mice treated with carboxy-PTIO (0.6 mg/kg) had dose-specifically reduced brain infarction, significantly by 27–30% (P < 0.05), even when therapy was delayed up to 4 h after the ischemic insult (P < 0.05). Four hour post-ischemia, ATP depleted in the ischemic hemisphere (P < 0.05). Administration with carboxy-PTIO not only improved the recovery of ATP in the ischemic hemisphere (P < 0.05), but also enhanced adenosine content across the ischemic and non-ischemic hemispheres (P < 0.05). The neuroprotection of carboxy-PTIO may be partly attributed to the beneficial effects of improving cerebral energy metabolism.
机译:我们检查了一氧化氮清除剂2-(4-羧基苯基)-4,4,5,5-四甲基咪唑啉-1-氧基1-3氧化物(羧基-PTIO)是否可以提供神经保护作用并改善脑能量代谢在中风模型中。 60只C57BL / 10J小鼠在永久性大脑中动脉闭塞0.5小时后腹膜内给予羧基-PTIO(0.3–1.2 mg / kg)或腹膜溶媒,以评估剂量反应效应。缺血后2-6小时,另外70只动物接受了羧基-PTIO(0.6 mg / kg)或赋形剂,以建立治疗窗口。用羧基-PTIO(0.6 mg / kg)或赋形剂处理的动物亚组用于测量脑生物能代谢产物(ATP,ADP,AMP,腺苷)。羧基-PTIO(0.6 mg / kg)治疗的小鼠具有剂量特异性地减少了脑梗塞,即使在缺血性损伤后最多延迟了4小时治疗后,其脑梗死也明显减少了27–30%(P <0.05)。 。缺血后四小时,缺血半球中的ATP耗尽(P <0.05)。羧基-PTIO给药不仅改善了缺血半球中ATP的回收率(P <0.05),而且还提高了缺血半球和非缺血半球中腺苷的含量(P <0.05)。羧基-PTIO的神经保护作用可能部分归因于改善脑能量代谢的有益作用。

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