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Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment

机译:缺血性卒中的辅助治疗方法:扩大治疗时间窗的创新

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Tissue plasminogen activator (tPA) thrombolysis remains the gold standard treatment for ischemic stroke. A time-constrained therapeutic window, with the drug to be given within 4.5 h after stroke onset, and lethal side effects associated with delayed treatment, most notably hemorrhagic transformation (HT), limit the clinical use of tPA. Co-administering tPA with other agents, including drug or non-drug interventions, has been proposed as a practical strategy to address the limitations of tPA. Here, we discuss the pharmacological and non-drug approaches that were examined to mitigate the complications?¢????especially HT?¢????associated with delayed tPA treatment. The pharmacological treatments include those that preserve the blood-brain barrier (e.g., atovarstatin, batimastat, candesartan, cilostazol, fasudil, minocycline, etc.), enhance vascularization and protect the cerebrovasculature (e.g., coumarin derivate IMM-H004 and granulocyte-colony stimulating factor (G-CSF)), and exert their effects through other modes of action (e.g., oxygen transporters, ascorbic acid, etc.). The non-drug approaches include stem cell treatments and gas therapy with multi-pronged biological effects. Co-administering tPA with the abovementioned therapies showed promise in attenuating delayed tPA-induced side effects and stroke-induced neurological and behavioral deficits. Thus, adjunctive treatment approach is an innovative therapeutic modality that can address the limitations of tPA treatment and potentially expand the time window for ischemic stroke therapy.
机译:组织纤溶酶原激活剂(tPA)溶栓仍是缺血性卒中的金标准治疗。具有时间限制的治疗窗口,在中风发作后4.5小时内给予药物,以及与延迟治疗相关的致死性副作用,最明显的是出血性转化(HT),限制了tPA的临床应用。已提出将tPA与其他药物(包括药物或非药物干预措施)共同给药作为解决tPA局限性的实用策略。在这里,我们讨论了为减轻并发症(尤其是HT)与延迟tPA治疗相关的并发症而研究的药理和非药物方法。药物治疗包括保留血脑屏障的药物(例如,阿托伐他汀,巴马司他,坎地沙坦,西洛他唑,法舒地尔,米诺环素等),增强血管生成和保护脑血管系统(例如香豆素衍生的IMM-H004和刺激粒细胞集落的作用) (G-CSF)),并通过其他作用方式(例如,氧气转运蛋白,抗坏血酸等)发挥作用。非药物方法包括干细胞治疗和具有多重生物学效应的气体治疗。将tPA与上述疗法合用显示出有望减轻tPA引起的延迟性副作用以及中风引起的神经和行为缺陷。因此,辅助治疗方法是一种创新的治疗方式,可以解决tPA治疗的局限性,并有可能扩大缺血性中风治疗的时间范围。

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