Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA
Stroke Vasc Neurol. 2024 Apr 30;9(2):97-107. doi: 10.1136/svn-2023-002363.
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.
本文重点探讨了基质金属蛋白酶-12（MMP-12）在缺血性中风（IS）中的新作用。IS 动物模型中大脑中 MMP-12 的表达显著增加，其抑制可减少脑损伤并促进神经、感觉运动和认知功能的恢复。因此，MMP-12 可能是 IS 治疗的潜在靶点。本文概述了 IS 后大脑中 MMP-12 的上调、其在中风后发病机制（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制见解、其与缺血后功能缺陷和恢复的关系，以及进一步研究的局限性、观点、挑战和未来方向。在对急性 IS 患者进行任何 MMP-12 靶向治疗之前，需要开展更多的研究，以确定 MMP-12 抑制对老年动物和合并症动物 IS 的有效性。本文还探讨了单独或联合抑制 MMP-9 对扩大目前有限的组织型纤溶酶原激活剂治疗时间窗的临床意义。靶向 MMP-12 有望对 IS 的治疗管理产生深远影响。
