Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients.
Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients.
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DOI：
10.3390/ijms222111622
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发表时间：
2021-10-27
影响因子：
5.6
通讯作者：
Pietras K
中科院分区：
文献类型：
--
作者：
Bocci M;Oudenaarden C;Sàenz-Sardà X;Simrén J;Edén A;Sjölund J;Möller C;Gisslén M;Zetterberg H;Englund E;Pietras K
广泛的神经系统表现与SARS-CoV-2感染后COVID-19的发展有关。然而，神经系统疾病的病因仍然是在很大程度上未被探索。在这里，我们使用了最先进的人脑多重免疫染色（n = 6 COVID-19，中位年龄= 69.5岁; n = 7对照，中位年龄= 68岁），并证明SARS-CoV-2受体ACE 2的表达仅限于神经血管周细胞的一个子集。引人注目的是，神经系统症状是独有的，普遍存在于血管周围细胞中ACE 2表达中度至高度的患者中。在血管壁和血管周围炎症中鉴定出病毒dsRNA，如T细胞和巨噬细胞浸润所示。此外，纤维蛋白原渗漏表明血脑屏障的完整性受损。值得注意的是，在SARS-CoV-2感染病例中，另外16名个体（n = 8名COVID-19，中位年龄= 67岁; n = 8名对照，中位年龄= 69.5岁）的脑脊液中周细胞标志物PDGFRβ水平显着较低，表明周细胞稳态被破坏。我们得出结论，SARS-CoV-2的周细胞感染是病毒进入特权中枢神经系统空间的基础，以及由于血管周围炎症和局部血脑屏障受损而引起的神经系统疾病。
A wide range of neurological manifestations have been associated with the development of COVID-19 following SARS-CoV-2 infection. However, the etiology of the neurological symptomatology is still largely unexplored. Here, we used state-of-the-art multiplexed immunostaining of human brains (n = 6 COVID-19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARS-CoV-2 receptor ACE2 is restricted to a subset of neurovascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macrophage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood–brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVID-19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRβ in SARS-CoV-2-infected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARS-CoV-2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised blood–brain barrier.
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DOI：
10.1016/s1474-4422(20)30308-2
发表时间：
2020-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Matschke J;Lütgehetmann M;Hagel C;Sperhake JP;Schröder AS;Edler C;Mushumba H;Fitzek A;Allweiss L;Dandri M;Dottermusch M;Heinemann A;Pfefferle S;Schwabenland M;Sumner Magruder D;Bonn S;Prinz M;Gerloff C;Püschel K;Krasemann S;Aepfelbacher M;Glatzel M
通讯作者：
Glatzel M
影响因子：
82.9
作者：
Su, Enming J.;Fredriksson, Linda;Lawrence, Daniel A.
通讯作者：
Lawrence, Daniel A.
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
5.5
作者：
Gallagher, PE;Chappell, MC;Tallant, EA
通讯作者：
Tallant, EA
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