Shah Kaushik, Abbruscato Thomas
Texas Tech University Health Sciences Center, 1300 S Coulter, School of Pharmacy, Department of Pharmaceutical Sciences.
Curr Pharm Des. 2014;20(10):1510-22. doi: 10.2174/13816128113199990465.
Cerebral ischemia is one of the major causes of disability worldwide. In cerebral ischemic stroke, occlusion of a major cerebral artery by an embolus or local thrombosis can result in transient or permanent reduction of cerebral blood flow to a portion of the brain, resulting in deprivation of glucose and oxygen. Since the brain relies on a continuous supply of nutrients and ions via mostly carrier mediated processes across the blood-brain barrier (BBB), any irregularity in these transport mechanisms dramatically affects neuronal function and outcome after acute and chronic stroke. Despite numerous encouraging breakthroughs in preclinical stroke studies that evaluate monotherapies and a prevailing neurocentric approach that has yielded disappointing clinical translation, preclinical stroke studies investigating additional therapeutic targets might be used more effectively in combination with thrombolysis. In this context, this current review discusses the current understanding of dysfunctionional BBB nutrient and ion transport mechanisms involved in stroke pathophsyiology as novel therapeutic approaches. Recognition of the important role of the neurovascular unit in pathophysiology of stroke will provide new opportunities to treat ischemic brain injury, and maintenance of nutrient and ionic homeostasis should facilitate brain repair after stroke.
脑缺血是全球致残的主要原因之一。在脑缺血性卒中中，栓子或局部血栓形成导致大脑主要动脉闭塞，可引起大脑部分区域的脑血流量短暂或永久性减少，导致葡萄糖和氧气供应不足。由于大脑主要通过载体介导的过程依赖血脑屏障（BBB）持续供应营养物质和离子，这些转运机制的任何异常都会显著影响急性和慢性卒中后的神经元功能和预后。尽管在评估单一疗法的临床前卒中研究中有许多令人鼓舞的突破，以及一种以神经为中心的主流方法却产生了令人失望的临床转化结果，但研究其他治疗靶点的临床前卒中研究可能与溶栓联合使用时更有效。在此背景下，本综述讨论了目前对参与卒中病理生理学的血脑屏障营养物质和离子转运功能障碍机制的理解，作为新的治疗方法。认识到神经血管单元在卒中病理生理学中的重要作用将为治疗缺血性脑损伤提供新的机会，维持营养物质和离子内环境稳定应有助于卒中后脑修复。
