Pathologically Entangled: Brain Trauma-Evoked ROS Imbalance Disrupts Kir Channel Function in Distant Peripheral Vessels.
Pathologically Entangled: Brain Trauma-Evoked ROS Imbalance Disrupts Kir Channel Function in Distant Peripheral Vessels.
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DOI：
10.1093/function/zqab021
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Longden TA
中科院分区：
文献类型：
--
作者：
Weir N;Longden TA
创伤性脑损伤（TBI）是发病的主要原因，并且由这种损伤引起的全身性炎症可导致对临床结果产生负面影响的各种进一步的病理。1.循环系统是一个巨大的网络，与每个组织和器官系统的细胞紧密交织在一起，因此可以作为一种载体，将造成损伤的物质从大脑中的原发部位运送到远处。重要的是，血管内皮--它在整个身体中形成一个连续的衬里，直接与血液接触--特别容易受到循环因子和细胞碎片的损伤。1是内向整流钾（K+）通道家族的成员，并且由毛细血管和小动脉内皮细胞（EC）表达。2该通道被细胞外K+和膜超极化激活3，并且需要膜磷脂，磷脂酰肌醇-4，5-二磷酸（PIP 2）来实现其活性。4因此，Kir 2通道在介导血管舒张对外部K+升高（例如在大脑活动或工作肌肉中发生的血管舒张）以及放大由广泛的其他血管舒张因素引起的膜超极化方面发挥着关键作用。对Kir 2的依赖。1对PIP 2的活性打开了血管系统，使其在创伤后具有潜在的脆弱性，因为PIP 2降解可响应于氧化应激或全身性炎症而发生，
Traumatic brain injury (TBI) is a leading cause of morbidity, and systemic inflammation resulting from such an insult can contribute to a variety of further pathologies that negatively impact clinical outcomes. 1 The circulatory system is a vast network that is tightly interwoven with the cells of every tissue and organ system, and thus can act as a vehicle conveying damagecausing agents from the primary site of injury in the brain to distant areas. Importantly, the vascular endothelium—which forms a continuous lining throughout the entire body that directly interfaces with the blood—is particularly vulnerable to damage resulting from circulating factors and cellular debris released in response to injury.Kir2. 1 is a member of the inward rectifier potassium (K+) channel family and is expressed by both capillary and arteriolar endothelial cells (ECs). 2 This channel is activated by both extracellular K+ and membrane hyperpolarization 3 and requires the membrane phospholipid, phosphatidylinositol-4, 5-bisphosphate (PIP2) for its activity. 4 As such, Kir2 channels play critical roles in mediating vasodilation to elevations of external K+, such as those that occur during brain activity or in working muscle, and in amplifying membrane hyperpolarization resulting from a broad range of other vasodilatory factors. The reliance of Kir2. 1 on PIP2 for its activity opens the vasculature up to potential vulnerabilities post-trauma, as PIP2 degradation can occur in response to oxidative stress or systemic inflammation,
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影响因子：
25
作者：
Longden TA;Dabertrand F;Koide M;Gonzales AL;Tykocki NR;Brayden JE;Hill-Eubanks D;Nelson MT
通讯作者：
Nelson MT
DOI：
10.1073/pnas.1800201115
发表时间：
2018-04-10
影响因子：
11.1
作者：
Harraz, Osama F.;Longden, Thomas A.;Nelson, Mark T.
通讯作者：
Nelson, Mark T.
影响因子：
9.8
作者：
He L;Vanlandewijck M;Mäe MA;Andrae J;Ando K;Del Gaudio F;Nahar K;Lebouvier T;Laviña B;Gouveia L;Sun Y;Raschperger E;Segerstolpe Å;Liu J;Gustafsson S;Räsänen M;Zarb Y;Mochizuki N;Keller A;Lendahl U;Betsholtz C
通讯作者：
Betsholtz C
影响因子：
5.5
作者：
Lamb, Iain R.;Novielli, Nicole M.;Murrant, Coral L.
通讯作者：
Murrant, Coral L.
影响因子：
4.2
作者：
Villalba, Nuria;Sackheim, Adrian M.;Freeman, Kalev
通讯作者：
Freeman, Kalev