Grape seed proanthocyanidins attenuate apoptosis in ischemic stroke.

Abstract

Grape seed proanthocyanidins (GSP) has been reported to attenuate endoplasmic reticulum (ER) stress-induced apoptosis, which is associated with ischemic stroke. However, whether GSP pays crucial roles in ischemic stroke still remains unclear. The purpose of this study is to explore the role of GSP in ischemic stroke and the underlying mechanism. The ischemic stroke mouse model was established by middle cerebral artery occlusion. GSP administration was performed intragastrically. Long-term neurological outcome was assessed by the foot fault test after reperfusion. Brain injury was identified by infarct volume from 2,3,5-triphenyltetrazolium chloride staining. Neuronal apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. The expression levels of Bax, Bcl-2, Cleaved Caspase-3, phosphorylated ERK (p-ERK), ERK, Glucose-regulated protein 78kDa (GRP78), Caspase-12 were detected by western blotting. In mice with ischemia stroke, GSP administration improved long-term neurological outcomes by attenuating ischemia-reperfusion induced neuronal apoptosis and brain injury. Mechanically, GSP performance inhibited the expression levels of ER stress-associated genes. GSP protects mice against ischemic stroke via attenuating neuronal apoptosis. Moreover, GSP attenuated ER stress-associated apoptosis by inhibiting GRP78 and Caspase-12. Our study indicates that GSP attenuates neuronal apoptosis in ischemic stroke, which shows the potential for ischemic stroke treatment.