Novel therpeautic interventions to treat ischemic stroke

治疗缺血性中风的新型治疗干预措施

基本信息

  • 批准号:
    10297858
  • 负责人:
  • 金额:
    $ 31.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-12-01 至 2023-11-30
  • 项目状态:
    已结题

项目摘要

Project Summary Stroke results in immense health and economic burden. Current strategies to improve stroke outcome is fibrinolysis of the clot with tissue plasminogen activator and mechanical thrombectomy, which involves reperfusion of the ischemic region. However, accumulating evidence suggests that cerebral reperfusion is often accompanied by oxidative stress, thrombosis, and vascular inflammation, which exacerbates neuronal death in the ischemic penumbra. There is currently no effective intervention available to protect the brain damage following reperfusion therapy. Clinical studies have shown a positive correlation between the massive influx of neutrophils and severity of injury following reperfusion. Integrin alpha9beta1 is highly expressed on neutrophils (relative to monocytes), upregulated upon activation and transmigration, and is known to stabilize neutrophil adhesion to activated endothelium in synergy with alpha2beta1 integrin. The mechanistic role of alpha9beta1 in stroke outcome is not explored yet. Utilizing novel mutant strains, in pilot studies, we found that alpha9beta1 exacerbates stroke outcome by modulating thrombosis and vascular inflammation. Following updated Stroke Therapy Academic Industry Roundtable (STAIR) pre-clinical guidelines and compelling pilot data, we propose to test the innovative hypothesis that integrin alpha9beta1 contributes to ischemic stroke exacerbation in stroke models with comorbidities and therapeutic targeting alpha9beta1 will improve stroke outcome by limiting thrombosis and inflammation. To accomplish this, we will utilize complementary genetic and pharmacological approaches, state-of-the-art intravital microscopy, magnetic resonance imaging, laser speckle imaging and follow current STAIR/RIGOR guidelines. Aging and biological sex are key determinants that influence stroke outcome. We will determine whether targeting alpha9beta1 will improve stroke outcome in the context of biological sex and aging so that the observed effect is generalizable to the broader context. This project may have significant clinical implications since understanding the mechanisms by which neutrophils contribute to reperfusion injury in stroke models with comorbidities may provide new therapeutic interventions to treat ischemic stroke.
项目摘要 中风造成巨大的健康和经济负担。目前改善卒中结局的策略是 使用组织纤溶酶原激活剂和机械血栓切除术(包括 缺血区域的再灌注。然而,越来越多的证据表明,脑再灌注是 通常伴有氧化应激、血栓形成和血管炎症, 在缺血半暗带死亡。目前还没有有效的干预措施来保护大脑 再灌注治疗后的损伤。临床研究表明, 再灌注后中性粒细胞的大量流入和损伤的严重程度。整合素α 9 β 1是高度 在中性粒细胞上表达(相对于单核细胞),在活化和迁移时上调, 已知与α 2 β 1整联蛋白协同作用稳定中性粒细胞粘附于活化的内皮。的 α 9 β 1在中风结果中的机械作用还没有研究。利用新的突变菌株,中试 研究中,我们发现α 9 β 1通过调节血栓形成和血管生成, 炎症根据更新的卒中治疗学术行业圆桌会议(STAIR)临床前 指南和令人信服的试点数据,我们建议测试创新的假设,整合素α 9 β 1 在伴有合并症和治疗靶向的卒中模型中导致缺血性卒中加重 α 9 β 1将通过限制血栓形成和炎症来改善中风结果。为了做到这一点,我们 将利用互补的遗传学和药理学方法,最先进的活体显微镜, 磁共振成像、激光散斑成像,并遵循当前的STAIR/RIGOR指南。老化和 生物学性别是影响卒中结局的关键决定因素。我们将决定是否针对 α 9 β 1将在生物性别和衰老的背景下改善卒中结局, 效果可以推广到更广泛的背景。该项目可能具有重要的临床意义, 了解中性粒细胞在卒中模型中促进再灌注损伤的机制, 合并症可能为缺血性卒中的治疗提供新的干预措施。

项目成果

期刊论文数量(0)
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Anil Kumar Chauhan其他文献

Rheological, Textural and Sensorial Properties of Quarg-Type Cheese Incorporated with Encapsulated <em>Terminalia Arjuna</em>
  • DOI:
    10.1016/j.focha.2023.100549
  • 发表时间:
    2024-06-01
  • 期刊:
  • 影响因子:
  • 作者:
    V.P. Aparnna;Anil Kumar Chauhan;Shubhendra Singh;Ravi Prakash;Pralay Maiti
  • 通讯作者:
    Pralay Maiti
Development of water spinach powder and its characterization
  • DOI:
    10.1007/s13197-021-05058-9
  • 发表时间:
    2021-03-09
  • 期刊:
  • 影响因子:
    3.300
  • 作者:
    Pallawi Joshi;Aparna Kumari;Anil Kumar Chauhan;Meenakshi Singh
  • 通讯作者:
    Meenakshi Singh
Quarg Cheese: The Impact of Fat Content Change on its Microstructure, Characterization, Rheology, and Textural Properties
夸格奶酪:脂肪含量变化对其微观结构、表征、流变学和质地特性的影响
A study on red potato peel (Solanum tuberosum L. cv. Red Holland): characterization, composition and formulation of tablet using different drying techniques
  • DOI:
    10.1007/s13197-024-06015-y
  • 发表时间:
    2024-06-17
  • 期刊:
  • 影响因子:
    3.300
  • 作者:
    Divya Tripathi;Muskan Kumari;Anil Kumar Chauhan;Dinesh Kumar;Madhukiran R. Dhondale
  • 通讯作者:
    Madhukiran R. Dhondale
A sustainable technology for enhancing the oxidative stability of edible oils using jackfruit (emArtocarpus heterophyllus/em lam.) peel extract as a natural antioxidant
一种利用菠萝蜜(Artocarpus heterophyllus Lam.)果皮提取物作为天然抗氧化剂来提高食用油氧化稳定性的可持续技术
  • DOI:
    10.1016/j.foodchem.2025.144564
  • 发表时间:
    2025-09-01
  • 期刊:
  • 影响因子:
    9.800
  • 作者:
    Rupali Koundal;Anil Kumar Chauhan;Rahul Das
  • 通讯作者:
    Rahul Das

Anil Kumar Chauhan的其他文献

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{{ truncateString('Anil Kumar Chauhan', 18)}}的其他基金

The University of Iowa Stroke Preclinical Assessment Network to Support Translational Studies for Acute Cerebroprotection
爱荷华大学中风临床前评估网络支持急性脑保护的转化研究
  • 批准号:
    10590946
  • 财政年份:
    2022
  • 资助金额:
    $ 31.43万
  • 项目类别:
The University of Iowa Stroke Preclinical Assessment Center for Neuroprotection in stroke
爱荷华大学中风临床前神经保护评估中心
  • 批准号:
    10200920
  • 财政年份:
    2019
  • 资助金额:
    $ 31.43万
  • 项目类别:
Novel therpeautic interventions to treat ischemic stroke
治疗缺血性中风的新型治疗干预措施
  • 批准号:
    10517515
  • 财政年份:
    2018
  • 资助金额:
    $ 31.43万
  • 项目类别:
Targeting Pyruvate Kinase M2: A novel strategy to combat thrombo-inflammation
靶向丙酮酸激酶 M2:对抗血栓炎症的新策略
  • 批准号:
    9905408
  • 财政年份:
    2018
  • 资助金额:
    $ 31.43万
  • 项目类别:
Novel therpeautic interventions to treat ischemic stroke
治疗缺血性中风的新型治疗干预措施
  • 批准号:
    10054977
  • 财政年份:
    2018
  • 资助金额:
    $ 31.43万
  • 项目类别:
Targeting Pyruvate Kinase M2: A novel strategy to combat thrombo-inflammation
靶向丙酮酸激酶 M2:对抗血栓炎症的新策略
  • 批准号:
    10600854
  • 财政年份:
    2018
  • 资助金额:
    $ 31.43万
  • 项目类别:
Targeting Pyruvate Kinase M2: A novel strategy to combat thrombo-inflammation
靶向丙酮酸激酶 M2:对抗血栓炎症的新策略
  • 批准号:
    10375485
  • 财政年份:
    2018
  • 资助金额:
    $ 31.43万
  • 项目类别:
Fibronectin alternative splicing in thrombosis and inflammation
纤连蛋白选择性剪接在血栓形成和炎症中的作用
  • 批准号:
    8787784
  • 财政年份:
    2014
  • 资助金额:
    $ 31.43万
  • 项目类别:
Fibronectin alternative splicing in thrombosis and inflammation
纤连蛋白选择性剪接在血栓形成和炎症中的作用
  • 批准号:
    8630620
  • 财政年份:
    2014
  • 资助金额:
    $ 31.43万
  • 项目类别:
Fibronectin alternative splicing in thrombosis and inflammation
纤连蛋白选择性剪接在血栓形成和炎症中的作用
  • 批准号:
    9199422
  • 财政年份:
    2014
  • 资助金额:
    $ 31.43万
  • 项目类别:

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