Hypoxic pre-conditioning suppresses experimental autoimmune encephalomyelitis by modifying multiple properties of blood vessels.
Hypoxic pre-conditioning suppresses experimental autoimmune encephalomyelitis by modifying multiple properties of blood vessels.
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DOI：
10.1186/s40478-018-0590-5
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发表时间：
2018-09-03
影响因子：
7.1
通讯作者：
Milner R
中科院分区：
文献类型：
--
作者：
Halder SK;Kant R;Milner R
虽然低氧预处理可以预防神经系统疾病，但其潜在机制尚未完全确定。由于慢性轻度缺氧（CMH，10%O2）触发中枢神经系统（CNS）的血管重塑，本研究的目的是研究缺氧预处理在多发性硬化（MS）的实验性自身免疫性脑脊髓炎（EAE）模型中的保护潜力，然后确定CMH如何影响EAE期间的血管完整性和潜在的细胞和分子机制。我们发现，在EAE诱导的同时暴露于CMH的小鼠被强烈地保护免受EAE进展的发展，如在临床水平和组织病理学水平上通过降低炎性白细胞浸润、血管破裂和脱髓鞘水平所评估的。从机制上讲，我们的研究表明，CMH保护，至少部分，通过增强血管的几个属性，有助于血管的完整性，包括减少表达的内皮细胞活化分子VCAM-1和ICAM-1，维持表达的内皮细胞紧密连接蛋白ZO-1和occludin，和上调表达的白细胞抑制蛋白层粘连蛋白-111血管基底膜。总之，这些数据表明，BBB完整性的优化是缺氧预处理的保护作用的重要机制。
While hypoxic pre-conditioning protects against neurological disease the underlying mechanisms have yet to be fully defined. As chronic mild hypoxia (CMH, 10% O2) triggers profound vascular remodeling in the central nervous system (CNS), the goal of this study was to examine the protective potential of hypoxic pre-conditioning in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) and then determine how CMH influences vascular integrity and the underlying cellular and molecular mechanisms during EAE. We found that mice exposed to CMH at the same time as EAE induction were strongly protected against the development of EAE progression, as assessed both at the clinical level and at the histopathological level by reduced levels of inflammatory leukocyte infiltration, vascular breakdown and demyelination. Mechanistically, our studies indicate that CMH protects, at least in part, by enhancing several properties of blood vessels that contribute to vascular integrity, including reduced expression of the endothelial activation molecules VCAM-1 and ICAM-1, maintained expression of endothelial tight junction proteins ZO-1 and occludin, and upregulated expression of the leukocyte inhibitory protein laminin-111 in the vascular basement membrane. Taken together, these data suggest that optimization of BBB integrity is an important mechanism underlying the protective effect of hypoxic pre-conditioning.
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影响因子：
9.3
作者：
Esen N;Katyshev V;Serkin Z;Katysheva S;Dore-Duffy P
通讯作者：
Dore-Duffy P
影响因子：
8.3
作者：
Dowden, J;Corbett, D
通讯作者：
Corbett, D
影响因子：
6.2
作者：
Li, Longxuan;Welser, Jennifer V.;Dore-Duffy, Paula;Del Zoppo, Gregory J.;Lamanna, Joseph C.;Milner, Richard
通讯作者：
Milner, Richard
影响因子：
5.3
作者：
Li, Longxuan;Liu, Fudong;Welser-Alves, Jennifer V.;McCullough, Louise D.;Milner, Richard
通讯作者：
Milner, Richard
影响因子：
5.3
作者：
Boroujerdi, Amin;Milner, Richard
通讯作者：
Milner, Richard