Fontes-Júnior Enéas Andrade, Maia Cristiane Socorro Ferraz, Fernandes Luanna Melo Pereira, Gomes-Leal Walace, Costa-Malaquias Allan, Lima Rafael Rodrigues, Prediger Rui Daniel, Crespo-López Maria Elena
Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil; Laboratory of Pharmacology of Inflammation and Behavior, Institute of Health Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
Laboratory of Pharmacology of Inflammation and Behavior, Institute of Health Sciences, Federal University of Pará, 66075-110 Belém, PA, Brazil.
Oxid Med Cell Longev. 2016;2016:1341453. doi: 10.1155/2016/1341453. Epub 2016 Jun 22.
Chronic alcohol intoxication (CAI) increases both morbidity and mortality of stroke patients. Despite the high prevalence of CAI and ischemic stroke, studies addressing their comorbidity and/or protective alternatives remain scarce. Thus, the influence of CAI on both stroke outcome and minocycline treatment (recognized for its neuroprotective effect) was investigated. Female Wistar rats (35 days old) were treated with water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days. Then, focal ischemia was induced by endothelin-1 in the motor cortex. Two hours later, four doses of 50 mg/kg of minocycline every 12 hours followed by five doses of 25 mg/kg every 24 hours were administered. Behavioral performance (open field and rotarod tests) and immunohistochemical (cellular density, neuronal death, and astrocytic activation) and biochemical (lipid peroxidation and nitrite levels) analyses were performed. CAI increased motor disruption, nitrite and lipid peroxidation levels, and neuronal loss caused by ischemia, whereas it reduced the astrogliosis. Minocycline was effective in preventing the motor and tissue damage caused by stroke. However, these effects were attenuated when CAI preceded stroke. Our data suggest that CAI beginning in adolescence contributes to a worse outcome in ischemic stroke survivors and reduces the benefits of minocycline, possibly requiring adjustments in therapy.
慢性酒精中毒（CAI）会增加中风患者的发病率和死亡率。尽管CAI和缺血性中风的患病率很高，但针对它们的合并症和/或保护性替代方案的研究仍然很少。因此，研究了CAI对中风结局和米诺环素治疗（因其神经保护作用而被认可）的影响。对35日龄的雌性Wistar大鼠用水或乙醇（6.5克/千克/天，22.5%重量/体积）处理55天。然后，通过内皮素-1在运动皮层诱导局灶性缺血。两小时后，每12小时给予四剂50毫克/千克的米诺环素，随后每24小时给予五剂25毫克/千克。进行行为表现（旷场试验和转棒试验）以及免疫组织化学（细胞密度、神经元死亡和星形胶质细胞活化）和生化（脂质过氧化和亚硝酸盐水平）分析。CAI增加了运动功能障碍、亚硝酸盐和脂质过氧化水平以及缺血引起的神经元损失，而它减少了星形胶质细胞增生。米诺环素可有效预防中风引起的运动和组织损伤。然而，当中风发生前存在CAI时，这些作用会减弱。我们的数据表明，青春期开始的CAI会导致缺血性中风幸存者的预后更差，并降低米诺环素的益处，可能需要调整治疗方案。
