Banks William A, Rhea Elizabeth M
Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA 98195, USA.
Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Antioxidants (Basel). 2021 Oct 27;10(11):1695. doi: 10.3390/antiox10111695.
The blood-brain barrier (BBB) is a network of specialized endothelial cells that regulates substrate entry into the central nervous system (CNS). Acting as the interface between the periphery and the CNS, the BBB must be equipped to defend against oxidative stress and other free radicals generated in the periphery to protect the CNS. There are unique features of brain endothelial cells that increase the susceptibility of these cells to oxidative stress. Insulin signaling can be impacted by varying levels of oxidative stress, with low levels of oxidative stress being necessary for signaling and higher levels being detrimental. Insulin must cross the BBB in order to access the CNS, levels of which are important in peripheral metabolism as well as cognition. Any alterations in BBB transport due to oxidative stress at the BBB could have downstream disease implications. In this review, we cover the interactions of oxidative stress at the BBB, how insulin signaling is related to oxidative stress, and the impact of the BBB in two diseases greatly affected by oxidative stress and insulin resistance: diabetes mellitus and Alzheimer's disease.
血脑屏障(BBB)是由特殊内皮细胞构成的网络,可调节底物进入中枢神经系统(CNS)。作为外周与CNS之间的界面,BBB必须具备抵御外周产生的氧化应激和其他自由基的能力,以保护CNS。脑内皮细胞具有独特特征,使其对氧化应激的易感性增加。胰岛素信号传导会受到不同水平氧化应激的影响,低水平氧化应激对信号传导是必需的,而高水平则有害。胰岛素必须穿过BBB才能进入CNS,其水平在外周代谢以及认知中都很重要。BBB处的氧化应激导致的BBB转运的任何改变都可能对下游疾病产生影响。在本综述中,我们阐述了BBB处氧化应激的相互作用、胰岛素信号传导与氧化应激的关系,以及BBB在受氧化应激和胰岛素抵抗影响极大的两种疾病——糖尿病和阿尔茨海默病中的作用。