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Stroke-induced brain parenchymal injury drives blood-brain barrier early leakage kinetics: a combined in vivo/in vitro study.卒中诱导的脑实质损伤驱动血脑屏障早期渗漏动力学:一项体内/体外联合研究。
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针对血脑屏障(BBB)的治疗方法,脑血管疾病溶栓治疗的先决条件——综述与进展

Targeting therapeutics across the blood brain barrier (BBB), prerequisite towards thrombolytic therapy for cerebrovascular disorders-an overview and advancements.

作者信息

Pulicherla K K, Verma Mahendra Kumar

机构信息

Center for Bioseparation Technology, VIT University, Vellore, Tamilnadu, India,

出版信息

AAPS PharmSciTech. 2015 Apr;16(2):223-33. doi: 10.1208/s12249-015-0287-z. Epub 2015 Jan 23.

DOI:10.1208/s12249-015-0287-z
PMID:25613561
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4370956/
Abstract

Cerebral tissues possess highly selective and dynamic protection known as blood brain barrier (BBB) that regulates brain homeostasis and provides protection against invading pathogens and various chemicals including drug molecules. Such natural protection strictly monitors entry of drug molecules often required for the management of several diseases and disorders including cerebral vascular and neurological disorders. However, in recent times, the ischemic cerebrovascular disease and clinical manifestation of acute arterial thrombosis are the most common causes of mortality and morbidity worldwide. The management of cerebral Ischemia requires immediate infusion of external thrombolytic into systemic circulation and must cross the blood brain barrier. The major challenge with available thrombolytic is their poor affinity towards the blood brain barrier and cerebral tissue subsequently. In the clinical practice, a high dose of thrombolytic often prescribed to deliver drugs across the blood brain barrier which results in drug dependent toxicity leading to damage of neuronal tissues. In recent times, more emphasis was given to utilize blood brain barrier transport mechanism to deliver drugs in neuronal tissue. The blood brain barrier expresses a series of receptor on membrane became an ideal target for selective drug delivery. In this review, the author has given more emphasis molecular biology of receptor on blood brain barrier and their potential as a carrier for drug molecules to cerebral tissues. Further, the use of nanoscale design and real-time monitoring for developed therapeutic to encounter drug dependent toxicity has been reviewed in this study.

摘要

脑组织具有高度选择性和动态性的保护机制,即血脑屏障(BBB),它调节脑内稳态,保护大脑免受入侵病原体和包括药物分子在内的各种化学物质的侵害。这种天然保护机制严格监控药物分子的进入,而药物分子对于包括脑血管疾病和神经疾病在内的多种疾病和病症的治疗往往是必需的。然而,近年来,缺血性脑血管疾病和急性动脉血栓形成的临床表现是全球范围内死亡和发病的最常见原因。脑缺血的治疗需要立即将外部溶栓剂注入体循环,且必须穿过血脑屏障。现有溶栓剂的主要挑战在于它们对血脑屏障和脑组织的亲和力较差。在临床实践中,通常会开出高剂量的溶栓剂以促使药物穿过血脑屏障,这会导致药物依赖性毒性,进而损害神经组织。近年来,人们更加重视利用血脑屏障转运机制将药物递送至神经组织。血脑屏障在膜上表达一系列受体,这使其成为选择性药物递送的理想靶点。在这篇综述中,作者更着重阐述了血脑屏障上受体的分子生物学及其作为药物分子向脑组织递送载体的潜力。此外,本研究还综述了利用纳米级设计和实时监测来开发治疗方法以应对药物依赖性毒性的情况。