MMP-12 对缺血性中风病理生理学的影响。

IF 4.4 1区 医学 Q1 CLINICAL NEUROLOGY
Krishna Kumar Veeravalli
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引用次数: 0

摘要

本文重点探讨基质金属蛋白酶-12(MMP-12)在缺血性中风(IS)中的新作用。在 IS 动物模型中,MMP-12 在大脑中的表达急剧增加,抑制 MMP-12 可减少脑损伤,促进神经、感觉运动和认知功能的恢复。因此,MMP-12 可能是治疗 IS 的潜在靶点。本文概述了 IS 后 MMP-12 在大脑中的上调情况、它在中风后发病机制(血脑屏障破坏、炎症、细胞凋亡和脱髓鞘)中的有害作用、可能的分子相互作用和机理认识、它在缺血后功能障碍和恢复中的参与以及进一步研究的局限性、前景、挑战和未来方向。在对急性IS患者进行任何MMP-12靶向疗法测试之前,还需要进行更多研究,以确定抑制MMP-12对老年动物和有合并症动物IS的有效性。本文还探讨了单独抑制 MMP-12 或与 MMP-9 联合使用对延长目前有限的组织纤溶酶原激活剂治疗时间窗的临床意义。以 MMP-12 为靶点有望在未来对 IS 的治疗管理产生深远影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Implications of MMP-12 in the pathophysiology of ischaemic stroke.

This article focuses on the emerging role of matrix metalloproteinase-12 (MMP-12) in ischaemic stroke (IS). MMP-12 expression in the brain increases dramatically in animal models of IS, and its suppression reduces brain damage and promotes neurological, sensorimotor and cognitive functional outcomes. Thus, MMP-12 could represent a potential target for the management of IS. This article provides an overview of MMP-12 upregulation in the brain following IS, its deleterious role in the post-stroke pathogenesis (blood-brain barrier disruption, inflammation, apoptosis and demyelination), possible molecular interactions and mechanistic insights, its involvement in post-ischaemic functional deficits and recovery as well as the limitations, perspectives, challenges and future directions for further research. Prior to testing any MMP-12-targeted therapy in patients with acute IS, additional research is needed to establish the effectiveness of MMP-12 suppression against IS in older animals and in animals with comorbidities. This article also examines the clinical implications of suppressing MMP-12 alone or in combination with MMP-9 for extending the currently limited tissue plasminogen activator therapy time window. Targeting of MMP-12 is expected to have a profound influence on the therapeutic management of IS in the future.

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来源期刊
Stroke and Vascular Neurology
Stroke and Vascular Neurology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
11.20
自引率
1.70%
发文量
63
审稿时长
15 weeks
期刊介绍: Stroke and Vascular Neurology (SVN) is the official journal of the Chinese Stroke Association. Supported by a team of renowned Editors, and fully Open Access, the journal encourages debate on controversial techniques, issues on health policy and social medicine.
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