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阿片受体拮抗剂作为缺血性脑卒中治疗的潜在药物。

Opioid antagonists as potential therapeutics for ischemic stroke.

机构信息

Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, USA; Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute of the University of Miami, USA.

Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, USA; Dr. JT Macdonald Foundation Biomedical Nanotechnology Institute of the University of Miami, USA.

出版信息

Prog Neurobiol. 2019 Nov;182:101679. doi: 10.1016/j.pneurobio.2019.101679. Epub 2019 Aug 6.

Abstract

Chronic use of prescription opioids exacerbates risk and severity of ischemic stroke. Annually, 6 million people die from stroke worldwide and there are no neuroprotective or neurorestorative agents to improve stroke outcomes and promote recovery. Prescribed opioids such as morphine have been shown to alter tight junction protein expression, resulting in the disruption of the blood brain barrier (BBB), ultimately leading to stroke pathogenesis. Consequently, protection of the BBB has been proposed as a therapeutic strategy for ischemic stroke. This perspective addresses the deficiency in stroke pharmacological options and examines a novel application and repurposing of FDA-approved opioid antagonists as a prospective neuroprotective therapeutic strategy to minimize BBB damage, reduce stroke severity, and promote neural recovery. Future directions discuss potential drug design and delivery methods to enhance these novel therapeutic targets.

摘要

慢性使用处方类阿片类药物会加剧缺血性中风的风险和严重程度。全球每年有 600 万人死于中风,目前尚无神经保护或神经修复药物来改善中风预后和促进康复。已证实,像吗啡这样的处方类阿片类药物会改变紧密连接蛋白的表达,从而破坏血脑屏障(BBB),最终导致中风的发病机制。因此,保护 BBB 已被提议作为缺血性中风的一种治疗策略。本观点讨论了中风药物治疗选择的不足,并研究了 FDA 批准的阿片类拮抗剂的新应用和再利用,作为一种有前景的神经保护治疗策略,以最大限度地减少 BBB 损伤、降低中风严重程度并促进神经恢复。未来的研究方向讨论了增强这些新型治疗靶点的潜在药物设计和给药方法。

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