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中华脑血管病杂志(电子版) ›› 2023, Vol. 17 ›› Issue (06) : 533 -538. doi: 10.11817/j.issn.1673-9248.2023.06.001

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血栓炎症在缺血性卒中发生发展机制中的研究进展
郑欣雅, 邱宝山, 王伊龙()   
  1. 100070 首都医科大学附属北京天坛医院神经病学中心
    100070 首都医科大学附属北京天坛医院神经病学中心;102206 北京脑科学与类脑研究所
    100070 首都医科大学附属北京天坛医院神经病学中心;102206 北京脑科学与类脑研究所;100070 北京,国家神经疾病医学中心
  • 收稿日期:2023-10-24 出版日期:2023-12-01
  • 通信作者: 王伊龙
  • 基金资助:
    国家自然科学基金委员会杰出青年科学基金项目(81825007); 北京高校卓越青年科学家计划项目(BJJWZYJH01201910025030)

Research progress on the mechanism of thromboinflammation in the occurrence and development of ischemic stroke

Xinya Zheng, Baoshan Qiu, Yilong Wang()   

  1. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
    Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;Chinese Institute for Brain Research, Beijing 102206, China
    Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;Chinese Institute for Brain Research, Beijing 102206, China;National Center for Neurological Disorders, Beijing 100070, China
  • Received:2023-10-24 Published:2023-12-01
  • Corresponding author: Yilong Wang
引用本文:

郑欣雅, 邱宝山, 王伊龙. 血栓炎症在缺血性卒中发生发展机制中的研究进展[J/OL]. 中华脑血管病杂志(电子版), 2023, 17(06): 533-538.

Xinya Zheng, Baoshan Qiu, Yilong Wang. Research progress on the mechanism of thromboinflammation in the occurrence and development of ischemic stroke[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2023, 17(06): 533-538.

在病理条件下,血管内皮细胞功能障碍触发凝血级联反应和炎症反应过程,其中,内皮细胞、血小板、白细胞之间的接触以及众多可溶性因子对细胞的调控将两个过程密切联系起来,共同构成“血栓炎症”过程。血栓炎症广泛参与了大动脉粥样硬化型缺血性卒中的发病、卒中急性期及再灌注损伤和卒中复发。了解血栓炎症在缺血性卒中中的作用对疾病的治疗和二级预防有重大意义,本文综述了血栓炎症作用机制及其在缺血性卒中发生发展中的研究进展。

Pathologically, vascular endothelial cell dysfunction leads to coagulation cascade and inflammatory processes. They are closely linked by both physical interactions and soluble factors regulation among endothelial cells, platelets, and white blood cells. Together, they constitute the process of "thromboinflammation". Thromboinflammation significantly contributes to the pathogenesis of large artery atherosclerotic ischemic stroke, acute stroke injury, and reperfusion injury, as well as stroke recurrence. Understanding the role of thromboinflammation in ischemic stroke is of great significance for the treatment and secondary prevention of the disease. This article reviews the recent research progress on the mechanism of thromboinflammation and its role in the development of ischemic stroke.

1
规范指导临床办公室国家百万减残工程, 中国老年医学学会脑血管病分会. 远隔缺血适应防治缺血性脑血管病中国专家共识 [J]. 中华医学杂志, 2021, 101(25): 1953-1967.
2
De Meyer SF, Denorme F, Langhauser F, et al. Thromboinflammation in stroke brain damage [J]. Stroke, 2016, 47(4): 1165-1172.
3
Stoll G, Nieswandt B. Thrombo-inflammation in acute ischaemic stroke-implications for treatment [J]. Nat Rev Neurol, 2019, 15(8): 473-481.
4
Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms [J]. Blood, 2019, 133(9): 906-918.
5
Pham M, Helluy X, Kleinschnitz C, et al. Sustained reperfusion after blockade of glycoprotein-receptor-Ib in focal cerebral ischemia: an MRI study at 17.6 Tesla [J]. PLoS One, 2011, 6(4): e18386.
6
Chou ML, Babamale AO, Walker TL, et al. Blood-brain crosstalk: the roles of neutrophils, platelets, and neutrophil extracellular traps in neuropathologies [J]. Trends Neurosci, 2023, 46(9): 764-779.
7
Stuckey SM, Ong LK, Collins-Praino LE, et al. Neuroinflammation as a key driver of secondary neurodegeneration following stroke? [J]. Int J Mol Sci, 2021, 22(23): 13101.
8
Constantinescu-Bercu A, Grassi L, Frontini M, et al. Activated α(IIb)β(3) on platelets mediates flow-dependent NETosis via SLC44A2 [J]. Elife, 2020, 9: e53353.
9
Müller F, Mutch NJ, Schenk WA, et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo [J]. Cell, 2009, 139(6): 1143-1156.
10
Sonnweber T, Pizzini A, Nairz M, et al. Arachidonic acid metabolites in cardiovascular and metabolic diseases [J]. Int J Mol Sci, 2018, 19(11): 3285.
11
Darbousset R, Thomas GM, Mezouar S, et al. Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation [J]. Blood, 2012, 120(10): 2133-2143.
12
Furie B, Furie BC. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation [J]. Trends Mol Med, 2004, 10(4): 171-178.
13
Asgari A, Jurasz P. Role of nitric oxide in megakaryocyte function [J]. Int J Mol Sci, 2023, 24(9): 8145.
14
Machlus KR, Johnson KE, Kulenthirarajan R, et al. CCL5 derived from platelets increases megakaryocyte proplatelet formation [J]. Blood, 2016, 127(7): 921-926.
15
Gorudko IV, Sokolov AV, Shamova EV, et al. Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry [J]. Biol Open, 2013, 2(9): 916-923.
16
Wagner DD, Heger LA. Thromboinflammation: from atherosclerosis to COVID-19 [J]. Arterioscler Thromb Vasc Biol, 2022, 42(9): 1103-1112.
17
Thiam HR, Wong SL, Wagner DD, et al. Cellular mechanisms of NETosis [J]. Annu Rev Cell Dev Biol, 2020, 36: 191-218.
18
Fuchs TA, Brill A, Duerschmied D, et al. Extracellular DNA traps promote thrombosis [J]. Proc Natl Acad Sci U S A, 2010, 107(36): 15880-15885.
19
Zhu C, Tian B. Intracranial atherosclerotic plaques identified on vessel wall imaging are associated with increased risk of first-ever stroke in a large Chinese cohort [J]. Eur J Neurol, 2023, 30(12): 3635-3636.
20
Roth S, Singh V, Tiedt S, et al. Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke [J]. Sci Transl Med, 2018, 10(432): eaao1313.
21
Zietz A, Gorey S, Kelly PJ, et al. Targeting inflammation to reduce recurrent stroke [J]. Int J Stroke, 2023: 17474930231207777.
22
Pircher J, Engelmann B, Massberg S, et al. Platelet-neutrophil crosstalk in atherothrombosis [J]. Thromb Haemost, 2019, 119(8): 1274-1282.
23
Libby P. Targeting inflammatory pathways in cardiovascular disease: the inflammasome, interleukin-1, interleukin-6 and beyond [J]. Cells, 2021, 10(4): 951.
24
Ridker PM. The time to initiate anti-inflammatory therapy for patients with chronic coronary atherosclerosis has arrived [J]. Circulation, 2023, 148(14): 1071-1073.
25
Braun LJ, Stegmeyer RI, Schäfer K, et al. Platelets docking to VWF prevent leaks during leukocyte extravasation by stimulating Tie-2 [J]. Blood, 2020, 136(5): 627-639.
26
Szepanowski RD, Haupeltshofer S, Vonhof SE, et al. Thromboinflammatory challenges in stroke pathophysiology [J]. Semin Immunopathol, 2023, 45(3): 389-410.
27
Zhang X, Gong P, Zhao Y, et al. Endothelial caveolin-1 regulates cerebral thrombo-inflammation in acute ischemia/reperfusion injury [J]. EBioMedicine, 2022, 84: 104275.
28
Cui J, Li H, Chen Z, et al. Thrombo-inflammation and immunological response in ischemic stroke: focusing on platelet-tregs interaction [J]. Front Cell Neurosci, 2022, 16: 955385.
29
Gill D, Veltkamp R. Dynamics of T cell responses after stroke [J]. Curr Opin Pharmacol, 2016, 26: 26-32.
30
Kleinschnitz C, Kraft P, Dreykluft A, et al. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature [J]. Blood, 2013, 121(4): 679-691.
31
Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology [J]. Physiol Rev, 2007, 87(1): 245-313.
32
Nieswandt B, Kleinschnitz C, Stoll G. Ischaemic stroke: a thrombo-inflammatory disease? [J]. J Physiol, 2011, 589(17): 4115-4123.
33
Santos-Lima B, Pietronigro EC, Terrabuio E, et al. The role of neutrophils in the dysfunction of central nervous system barriers [J]. Front Aging Neurosci, 2022, 14: 965169.
34
戚智锋, 罗玉敏, 刘克建. 自由基和基质金属蛋白酶介导脑缺血血脑屏障损伤的研究进展 [J]. 生物物理学报, 2012, 28(5): 383-391.
35
Stark K, Massberg S. Interplay between inflammation and thrombosis in cardiovascular pathology [J]. Nat Rev Cardiol, 2021, 18(9): 666-682.
36
Zhang Z, Shen C, Fang M, et al. Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke [J]. Cell Mol Life Sci, 2022, 79(5): 240.
37
Hernández-Jiménez M, Abad-Santos F, Cotgreave I, et al. Safety and efficacy of ApTOLL in patients with ischemic stroke undergoing endovascular treatment: a phase 1/2 randomized clinical trial [J]. JAMA Neurol, 2023, 80(8): 779-788.
38
Ramiro L, Simats A, García-Berrocoso T, et al. Inflammatory molecules might become both biomarkers and therapeutic targets for stroke management [J]. Ther Adv Neurol Disord, 2018, 11: 1756286418789340.
39
贾建平, 陈生弟. 神经病学 [M]. 8版. 北京: 人民卫生出版社, 2021: 204-207.
40
McCabe JJ, Camps-Renom P, Giannotti N, et al. Carotid plaque inflammation imaged by PET and prediction of recurrent stroke at 5 years [J]. Neurology, 2021, 97(23): e2282-e2291.
41
Foschi M, Padroni M, Abu-Rumeileh S, et al. Diagnostic and prognostic blood biomarkers in transient ischemic attack and minor ischemic stroke: an up-to-date narrative review [J]. Stroke Cerebrovasc Dis, 2022, 31(3): 106292.
42
Yang M, Pan Y, Li Z, et al. Platelet count predicts adverse clinical outcomes after ischemic stroke or TIA: subgroup analysis of CNSR II [J]. Front Neurol, 2019, 10: 370.
43
Whiteley W, Wardlaw J, Dennis M, et al. Blood biomarkers for the diagnosis of acute cerebrovascular diseases: a prospective cohort study [J]. Cerebrovasc Dis, 2011, 32(2): 141-147.
44
Khandkar C, Vaidya K, Patel S. Colchicine for stroke prevention: a systematic review and meta-analysis [J]. Clin Ther, 2019, 41(3): 582-590.
45
Wang Y, Li J, Johnston SC, et al. Colchicine in high-risk patients with acute minor-to-moderate ischemic stroke or transient ischemic attack (CHANCE-3): rationale and design of a multicenter randomized placebo-controlled trial [J]. Int J Stroke, 2023, 18(7): 873-878.
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