Aging, the metabolic syndrome, and ischemic stroke: redefining the approach for studying the blood-brain barrier in a complex neurological disease.
Aging, the metabolic syndrome, and ischemic stroke: redefining the approach for studying the blood-brain barrier in a complex neurological disease.
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DOI：
10.1016/bs.apha.2014.07.001
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Huber, Jason D
中科院分区：
文献类型：
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作者：
Lucke-Wold, Brandon P;Logsdon, Aric F;Huber, Jason D
血脑屏障（BBB）在维持大脑的免疫特权状态方面具有许多重要功能。内皮细胞、星形胶质细胞和周细胞在保持脉管系统完整性方面发挥着重要作用。随着年龄的增长，细胞衰老会导致血脑屏障受损。受损的血脑屏障使得炎症细胞因子大量涌入大脑。这些细胞因子导致神经元和神经胶质损伤。最终，大脑内的功能变化可能导致与年龄相关的疾病。最突出的与年龄相关的疾病之一是缺血性中风。中风是美国最大的残疾原因，也是第三大死亡原因。除了年龄之外，中风的最大危险因素是代谢综合征的结果。如果不加以控制，代谢综合征会迅速发展为糖尿病、高血压、心血管疾病和肥胖等后果。这些合并症对 BBB 损害的贡献是巨大的。一些常见的激活分子途径包括：内质网应激、活性氧形成和谷氨酸兴奋毒性。在本章中，我们研究中枢神经系统内细胞的年龄相关变化如何与合并症相互作用。然后我们研究合并症如何通过血脑屏障破坏导致中风风险增加。最后，我们讨论了感兴趣的关键分子途径，重点关注值得进一步研究的治疗靶点。
The blood-brain barrier (BBB) has many important functions in maintaining the brain's immune-privileged status. Endothelial cells, astrocytes, and pericytes have important roles in preserving vasculature integrity. As we age, cell senescence can contribute to BBB compromise. The compromised BBB allows an influx of inflammatory cytokines to enter the brain. These cytokines lead to neuronal and glial damage. Ultimately, the functional changes within the brain can cause age-related disease. One of the most prominent age-related diseases is ischemic stroke. Stroke is the largest cause of disability and is third largest cause of mortality in the United States. The biggest risk factors for stroke, besides age, are results of the metabolic syndrome. The metabolic syndrome, if unchecked, quickly advances to outcomes that include diabetes, hypertension, cardiovascular disease, and obesity. The contribution from these comorbidities to BBB compromise is great. Some of the common molecular pathways activated include: endoplasmic reticulum stress, reactive oxygen species formation, and glutamate excitotoxicity. In this chapter, we examine how age-related changes to cells within the central nervous system interact with comorbidities. We then look at how comorbidities lead to increased risk for stroke through BBB disruption. Finally, we discuss key molecular pathways of interest with a focus on therapeutic targets that warrant further investigation.