Recent studies have shown that obesity and its related metabolic dysfunction exacerbate outcomes of ischemic brain injuries in some brain areas, such as the hippocampus and cerebral cortex when they are subjected to transient ischemia. However, the impact of obesity in the striatum after brief transient ischemia has not yet been addressed. The objective of this study was to investigate effects of obesity on neuronal damage and inflammation in the striatum after transient ischemia and to examine the role of mTOR which is involved in the pathogenesis of metabolic and neurological diseases. Gerbils were fed with normal diet (ND) or high-fat diet (HFD) for 12 weeks and subjected to 5 min of transient ischemia. HFD-fed gerbils showed significant increase in body weight, blood glucose level, serum triglycerides, total cholesterol and low-density lipoprotein cholesterol without affecting food intake. Neuronal death/loss in the HFD-fed gerbils occurred in the dorsolateral striatum 2 days after transient ischemia, and neuronal loss was increased 5 days after transient ischemia, although no neuronal loss was observed in ND-fed gerbils at any time after transient ischemia. The HFD-fed gerbils showed hypertrophied microglia and further increased expressions of tumor necrosis factor-alpha, interukin-1beta, mammalian target of rapamycin (mTOR) and phosphorylated-mTOR during pre- and post-ischemic phases compared with the ND-fed gerbils. Additionally, we found that treatment with mTOR inhibitor rapamycin in the HFD-fed gerbils significantly attenuated transient ischemia-induced neuronal death in the dorsolateral striatum. These findings reveal that chronic HFD-induced obesity results in severe neuroinflammation and significant increase of mTOR activation, which could contribute to neuronal death in the stratum following 5 min of transient ischemia. Especially, abnormal mTOR activation would play a key role in mediating obesity-induced severe ischemic brain injury.

最近的研究表明，肥胖症及其相关的代谢功能障碍会加重某些大脑区域（如海马和大脑皮层）遭受短暂性缺血后缺血性脑损伤的后果。然而，短暂短暂性脑缺血后肥胖对纹状体的影响尚未得到解决。这项研究的目的是调查肥胖对短暂性脑缺血后纹状体神经元损伤和炎症的影响，并研究mTOR在代谢和神经系统疾病发病机理中的作用。给沙鼠喂食正常饮食（ND）或高脂饮食（HFD）12周，并进行5分钟的短暂性缺血。由HFD喂养的沙鼠的体重，血糖水平，血清甘油三酸酯，总胆固醇和低密度脂蛋白胆固醇，而不会影响食物的摄入。短暂性脑缺血后2天，HFD喂养的沙鼠的神经元死亡/损失发生在背外侧纹状体，短暂性脑缺血后5天，神经元的损失增加，尽管在短暂性脑缺血后的任何时间，ND喂养的沙鼠均未观察到神经元的损失。与ND喂养的沙鼠相比，HFD喂养的沙鼠表现出肥大的小胶质细胞，并且在缺血前和缺血后阶段，肿瘤坏死因子-α，interukin-1beta，雷帕霉素的哺乳动物靶标（mTOR）和磷酸化的mTOR的表达进一步增加。此外，我们发现，在喂食HFD的沙鼠中使用mTOR抑制剂雷帕霉素进行治疗可显着减轻背侧纹状体短暂性缺血诱导的神经元死亡。这些发现表明，慢性HFD引起的肥胖症会导致严重的神经炎症和mTOR激活的显着增加，这可能会导致短暂性缺血5分钟后地层中的神经元死亡。特别是，mTOR异常激活在介导肥胖引起的严重缺血性脑损伤中起关键作用。