Rivera Felicia, Costa Gustavo, Abin Andrés, Urbanavicius Jessika, Arruti Cristina, Casanova Gabriela, Dajas Federico
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Neurotox Res. 2008 Apr;13(2):105-14. doi: 10.1007/BF03033562.
Oxidative stress is implicated in the pathogenesis of cerebral ischemia injury, and the flavonoids have shown to be neuroprotective in experimental models of cerebral ischemia. Previously, we have shown that an aqueous preparation of quercetin did not reach the brain while a liposomal preparation produced measurable cerebral amounts of quercetin that reduced significantly the cerebral damage provoked by permanent middle cerebral artery occlusion (pMCAo) of rats. In this context, the protective effects of liposomal quercetin (LQ) were investigated in the same model after 1 and 4 hours of arterial occlusion. LQ was administered in a single dose (30 mg/kg), at 30 min, 1 and 4 h after pMCAo, and the brain was studied 24 h later. Cerebral damage and the oedema volume were assessed with a tetrazolium salt (TTC). The status of brain tissue, the neuronal population, the global motor behaviour as well as the antioxidant, endogenous reduced glutathione (GSH), were also assessed in the brain. Thirty min after LQ there was a significantly protective effect against ischemic lesion demonstrated by a significant increase in numbers of cells in striatum and cortex, together with a partial reversal of motor deficits. GSH levels decreased after ischemia in ipsilateral striatum and cortex, and the LQ preparation reversed these effects 24 h after the occlusion. Our results suggest that endogenous brain GSH is critical in the defense mechanisms after ischemia, as a significant mediator of the protective effects of the LQ preparation.
氧化应激与脑缺血损伤的发病机制有关，黄酮类化合物在脑缺血实验模型中已显示出神经保护作用。此前，我们已经表明，槲皮素的水制剂无法到达脑部，而脂质体制剂可使脑部产生可测量的槲皮素量，显著减少大鼠永久性大脑中动脉闭塞（pMCAo）引起的脑损伤。在此背景下，我们在动脉闭塞1小时和4小时后的同一模型中研究了脂质体槲皮素（LQ）的保护作用。在pMCAo后30分钟、1小时和4小时，以单剂量（30mg/kg）给予LQ，24小时后对脑部进行研究。用四氮唑盐（TTC）评估脑损伤和水肿体积。还评估了脑组织状态、神经元数量、整体运动行为以及脑内抗氧化剂、内源性还原型谷胱甘肽（GSH）的情况。给予LQ 30分钟后，对缺血性损伤有显著的保护作用，表现为纹状体和皮质中的细胞数量显著增加，同时运动功能障碍部分逆转。缺血后同侧纹状体和皮质中的GSH水平降低，而LQ制剂在闭塞24小时后逆转了这些作用。我们的结果表明，脑内源性GSH在缺血后的防御机制中至关重要，是LQ制剂保护作用的重要介导因子。
