Center for Genetic Engineering and Biotechnology, Pharmaceutical Division, Cubanacan, Playa, La Habana, Cuba.
Restor Neurol Neurosci. 2013;31(2):213-23. doi: 10.3233/RNN-120262.
Stroke is the second cause of mortality worldwide, with a high incidence of disability in survivors. Promising candidate drugs have failed in stroke trials. Combined therapies are attractive strategies that simultaneously target different points of stroke pathophysiology. The aim of this work is to determine whether the combined effects of epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP6) can attenuate clinical signs and pathology in an experimental stroke model.
Brain global ischemia was generated in Mongolian gerbils by 15 minutes of carotid occlusion. After reperfusion, EGF, GHRP6 or EGF+GHRP6 were intraperitoneally administered. Clinical manifestations were monitored daily. Three days after reperfusion, animals were anesthetized and perfused with an ink solution. The anatomy of the Circle of Willis was characterized. Infarct volume and neuronal density were analyzed.
EGF+GHRP6 co-administration reduced clinical manifestations and infarct volume and preserved neuronal density. No correlation was observed between the grade of anastomosis of the Circle of Willis and clinical manifestations in the animals receiving EGF+GHRP6, as opposed to the vehicle-treated gerbils.
Co-treatment with EGF and GHRP6 affects both the clinical and pathological outcomes in a global brain ischemia model, suggesting a suitable therapeutic approach for the acute management of stroke.
卒中是全球第二大致死原因，幸存者致残率高。有前途的候选药物在卒中试验中失败。联合治疗是一种有吸引力的策略，可同时针对卒中病理生理学的不同靶点。本研究旨在确定表皮生长因子（EGF）和生长激素释放肽-6（GHRP6）联合是否能减轻实验性卒中模型中的临床症状和病理。
通过 15 分钟的颈总动脉闭塞，在蒙古沙鼠中产生全脑缺血。再灌注后，腹腔内给予 EGF、GHRP6 或 EGF+GHRP6。每天监测临床表现。再灌注后 3 天，动物麻醉并用墨汁溶液灌注。描述 Willis 环的解剖结构。分析梗死体积和神经元密度。
EGF+GHRP6 联合给药可减轻临床症状、梗死体积并保护神经元密度。与接受 EGF+GHRP6 治疗的动物相比，在接受载体治疗的沙鼠中，Willis 环吻合程度与临床症状之间没有相关性。
EGF 和 GHRP6 联合治疗可影响全脑缺血模型的临床和病理结局，提示这是一种治疗急性卒中的合适方法。
