Emergent Uric Acid Treatment is Synergistic with Mechanical Recanalization in Improving Stroke Outcomes in Male and Female Rats
Emergent Uric Acid Treatment is Synergistic with Mechanical Recanalization in Improving Stroke Outcomes in Male and Female Rats
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DOI：
10.1016/j.neuroscience.2018.07.045
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发表时间：
2018-09-15
期刊：
影响因子：
3.3
通讯作者：
Salom, Juan B.
中科院分区：
文献类型：
--
作者：
Aliena-Valero, Alicia;Lopez-Morales, Mikahela A.;Salom, Juan B.
临床前和临床研究支持在缺血性卒中中紧急给予尿酸（UA）具有有希望的神经保护作用，尽管不是确定的。我们评估了UA在缺血性卒中模型中的作用，该模型与STAIR/RIGOR推荐的机械血栓切除术的当前治疗模式相关。一组雄性和雌性Wistar大鼠在生理监测下进行缺血性卒中和机械再通。在24 h和7天时评估了短暂性大脑中动脉闭塞（tMCAO）与连续性UA（IV，16 mg/kg）或溶剂处理的影响。结果包括神经功能损害、脑梗死（TTC染色、MRI成像和甲酚紫染色）和水肿。在tMCAO后24小时，神经功能评分和脑梗死的大鼠进行UA治疗相比，车辆显着减少，与选择性作用的UA皮质梗死。雄鼠和雌鼠之间UA的作用没有差异，因为性别与卒中结局之间没有显著的相互作用。大鼠在tMCAO后达到较高的再灌注水平，显示出UA对神经功能损害、皮质梗死和水肿的上级减少。在7天的随访后，与溶剂治疗相比，接受UA治疗的雄性大鼠仍然显示出神经功能损伤和梗死面积的减少。总之，短暂性脑缺血后立即进行UA治疗，可使脑损伤和神经功能缺损持续减少，且与性别无关，在高灌注状态下表现更好。UA与机械再通的协同效应支持UA作为机械血栓切除术的后续治疗的额外临床试验。(C)2018年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Preclinical and clinical studies support a promising, albeit not definitive, neuroprotective effect of emergent uric acid (UA) administration in ischemic stroke. We assessed the effects of UA in an ischemic stroke model relevant to the current treatment paradigm of mechanical thrombectomy within the STAIR/RIGOR recommendations. A cohort of male and female Wistar rats was subjected to ischemic stroke with mechanical recanalization under physiological monitoring. The effects of transient middle cerebral artery occlusion (tMCAO) with adjunctive UA (IV, 16 mg/kg) or vehicle treatment were assessed at 24 h and 7 days. Outcomes included neurofunctional impairment, brain infarct (TTC staining, MRI imaging and cresyl violet staining) and edema. At 24 h after tMCAO, neurofunctional scores and brain infarct were significantly reduced in rats subjected to UA treatment compared to vehicle, with a selective effect of UA on cortical infarct. No differential effect of UA between male and female rats was evidenced, as no significant interaction of sex with stroke outcomes was found. Rats achieving higher reperfusion levels after tMCAO showed superior reduction of neurofunctional impairment, cortical infarct and edema by UA. After a 7-day follow-up, male rats subjected to UA treatment still showed reductions in neurofunctional impairment and infarct size, compared to vehicle treatment. In conclusion, UA treatment immediately after transient ischemia results in a sex-independent, maintained reduction of brain damage and neurological impairment, better manifested in hyperperfusion conditions. This synergistic effect of UA with mechanical recanalization supports additional clinical testing of UA as an adjunctive treatment to mechanical thrombectomy. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.