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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小时的治疗机会,并防止小鼠永久性局灶性脑缺血后缺血引起的能量消耗。

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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-L:-氧-3-氧化物(羧基-PTIO)是否可以提供神经保护作用并改善大脑能量中风模型中的新陈代谢。 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)或赋形剂,以评估剂量反应效应。在缺血后2-6小时,另外70只动物接受羧基-PTIO(0.6mg / kg)或媒介,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)。用羧基-PTIO(0.6 mg / kg)治疗的小鼠具有剂量特异性地减少了脑梗塞,即使缺血性损伤后最多延迟了4小时治疗也显着降低了27-30%(P <0.05)(P <0.05) 。缺血后四小时,缺血半球中的ATP耗尽(P <0.05)。用羧基-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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