Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA; Tulane Brain Institute, Tulane University, New Orleans, LA 70112, USA.
Exp Neurol. 2020 Sep;331:113323. doi: 10.1016/j.expneurol.2020.113323. Epub 2020 Apr 19.
Ischemic stroke is a leading cause of death and disability worldwide. Currently, the only pharmacological therapy for ischemic stroke is thrombolysis with tissue plasminogen activator that has a narrow therapeutic window and increases the risk of intracerebral hemorrhage. New pharmacological treatments for ischemic stroke are desperately needed, but no neuroprotective drugs have successfully made it through clinical trials. Beneficial effects of peroxisome proliferator-activated receptor alpha (PPARα) activation on vascular integrity and function have been reported, and PPARα agonists have clinically been used for many years to manage cardiovascular disease. Thus, PPARα has gained interest in recent years as a target for neurovascular disease such as ischemic stroke. Accumulating preclinical evidence suggests that PPARα activation modulates several pathophysiological hallmarks of stroke such as oxidative stress, blood-brain barrier (BBB) dysfunction, and neuroinflammation to improve functional recovery. Therefore, this review summarizes the various actions PPARα exerts in neurovascular health and disease and the potential of employing exogenous PPARα agonists for future pharmacological treatment of ischemic stroke.
缺血性脑卒中是全球范围内主要的致死和致残原因。目前，缺血性脑卒中唯一的药物治疗方法是使用组织型纤溶酶原激活物进行溶栓治疗，但该方法治疗窗口较窄，且会增加颅内出血的风险。因此，急需新的药物治疗方法，但没有神经保护药物成功通过临床试验。已有研究报道过过氧化物酶体增殖物激活受体α（PPARα）激活对血管完整性和功能的有益作用，PPARα 激动剂已在临床上使用多年来治疗心血管疾病。因此，近年来，PPARα 作为缺血性脑卒中等神经血管疾病的靶点引起了人们的兴趣。越来越多的临床前证据表明，PPARα 激活可调节氧化应激、血脑屏障（BBB）功能障碍和神经炎症等多种与中风相关的病理生理特征，从而改善功能恢复。因此，本综述总结了 PPARα 在神经血管健康和疾病中的各种作用，以及使用外源性 PPARα 激动剂作为缺血性脑卒中未来药物治疗的潜力。
