Oliveira Gedeão Batista, Fontes Enéas de Andrade, de Carvalho Sabrina, da Silva Josiane Batista, Fernandes Luanna Melo Pereira, Oliveira Maria Cristina Souza Pereira, Prediger Rui Daniel, Gomes-Leal Walace, Lima Rafael Rodrigues, Maia Cristiane Socorro Ferraz
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
Programa de Pós-graduação em Neurociências e Biologia Celular, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-900 Belém, Pará, Brazil.
Brain Res. 2014 May 2;1561:23-34. doi: 10.1016/j.brainres.2014.03.005. Epub 2014 Mar 15.
Ethanol is an important risk factor for the occurrence of cerebral ischemia contributing to poor prognosis and inefficacy of drug treatments for stroke-related symptoms. Females have a higher lifetime risk for stroke than males. Moreover, female gender has been associated with increased ethanol consumption during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence may potentiate the motor impairments and cortical damage induced by focal ischemia in female rats. We also addressed whether these effects can be mitigated by minocycline, which has been shown to be neuroprotective against different insults in the CNS. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days by gavage. Focal ischemia was induced by microinjections of endothelin-1 (ET-1) into the motor cortex. Animals of both groups were treated daily with minocycline (25-50 mg/kg, i.p.) or sterile saline (i.p.) for 5 days, and motor function was assessed using open field, inclined plane and rotarod tests. Chronic ethanol exposure exacerbated locomotor activity and motor coordination impairments induced by focal ischemia in rats. Moreover, histological analysis revealed that microinjections of ET-1 induced pyramidal neuron loss and microglial activation in the motor cortex. Minocycline reversed the observed motor impairments, microglial activation and pyramidal neuron loss in the motor cortex of ischemic rats even in those exposed to ethanol. These results suggest that minocycline induces neuroprotection and functional recovery in ischemic female rats intoxicated with ethanol during adolescence. Furthermore, the mechanism underlying this protective effect may be related to the modulation of neuroinflammation.
乙醇是导致脑缺血发生的重要风险因素，会导致预后不良以及中风相关症状的药物治疗效果不佳。女性一生中患中风的风险高于男性。此外，女性在青春期的乙醇摄入量增加。在本研究中，我们调查了青春期慢性乙醇暴露是否会加重雌性大鼠局灶性缺血诱导的运动障碍和皮质损伤。我们还探讨了米诺环素是否可以减轻这些影响，米诺环素已被证明对中枢神经系统的不同损伤具有神经保护作用。通过灌胃法给雌性大鼠用蒸馏水或乙醇（6.5克/千克/天，22.5%重量/体积）处理55天。通过向运动皮层微量注射内皮素-1（ET-1）诱导局灶性缺血。两组动物每天用米诺环素（25-50毫克/千克，腹腔注射）或无菌生理盐水（腹腔注射）处理5天，并使用旷场试验、斜面试验和转棒试验评估运动功能。慢性乙醇暴露加剧了大鼠局灶性缺血诱导的运动活动和运动协调障碍。此外，组织学分析显示，微量注射ET-1会导致运动皮层锥体细胞丢失和小胶质细胞活化。米诺环素逆转了缺血大鼠运动皮层中观察到的运动障碍、小胶质细胞活化和锥体细胞丢失，即使是在暴露于乙醇的大鼠中也是如此。这些结果表明，米诺环素可诱导青春期乙醇中毒的缺血雌性大鼠产生神经保护作用并实现功能恢复。此外，这种保护作用的潜在机制可能与神经炎症的调节有关。
