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具有缺血性中风治疗潜力的药理学策略的开发。

Development of Pharmacological Strategies with Therapeutic Potential in Ischemic Stroke.

作者信息

Escobar-Peso Alejandro, Martínez-Alonso Emma, Masjuan Jaime, Alcázar Alberto

机构信息

Department of Research, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.

Department of Neurology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.

出版信息

Antioxidants (Basel). 2023 Dec 12;12(12):2102. doi: 10.3390/antiox12122102.

Abstract

Acute ischemic stroke constitutes a health challenge with great social impact due to its high incidence, with the social dependency that it generates being an important source of inequality. The lack of treatments serving as effective neuroprotective therapies beyond thrombolysis and thrombectomy is presented as a need. With this goal in mind, our research group's collaborative studies into cerebral ischemia and subsequent reperfusion concluded that there is a need to develop compounds with antioxidant and radical scavenger features. In this review, we summarize the path taken toward the identification of lead compounds as potential candidates for the treatment of acute ischemic stroke. Evaluations of the antioxidant capacity, neuroprotection of primary neuronal cultures and in vivo experimental models of cerebral ischemia, including neurological deficit score assessments, are conducted to characterize the biological efficacy of the various neuroprotective compounds developed. Moreover, the initial results in preclinical development, including dose-response studies, the therapeutic window, the long-term neuroprotective effect and in vivo antioxidant evaluation, are reported. The results prompt these compounds for clinical trials and are encouraging regarding new drug developments aimed at a successful therapy for ischemic stroke.

摘要

急性缺血性中风因其高发病率而构成一项具有重大社会影响的健康挑战,它所导致的社会依赖性是不平等的一个重要根源。除了溶栓和取栓治疗外,缺乏有效的神经保护疗法成为一种需求。出于这一目标,我们研究小组对脑缺血及随后的再灌注进行的合作研究得出结论,需要开发具有抗氧化和自由基清除特性的化合物。在这篇综述中,我们总结了在确定先导化合物作为治疗急性缺血性中风潜在候选药物方面所采取的路径。对各种开发的神经保护化合物的生物功效进行了评估,包括抗氧化能力评估、原代神经元培养物的神经保护作用以及脑缺血的体内实验模型评估,其中包括神经功能缺损评分评估。此外,还报告了临床前开发的初步结果,包括剂量反应研究、治疗窗口、长期神经保护作用和体内抗氧化评估。这些结果促使这些化合物进入临床试验,并且对于旨在成功治疗缺血性中风的新药开发而言是令人鼓舞的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/10740896/3c9a0e3df9e9/antioxidants-12-02102-sch001.jpg

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