Open AccessOsteopontin attenuates early brain injury through regulating autophagy‐apoptosis interaction after subarachnoid hemorrhage in rats
Author(s) -
Sun ChengMei,
Enkhjargal Budbazar,
Reis Cesar,
Zhou KeRen,
Xie ZhiYi,
Wu LingYun,
Zhang TongYu,
Zhu QiQuan,
Tang JiPing,
Jiang XiaoDan,
Zhang John H.
Publication year - 2019
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13199
Subject(s) - autophagy , atg5 , osteopontin , apoptosis , endogeny , subarachnoid hemorrhage , medicine , microbiology and biotechnology , chemistry , pharmacology , endocrinology , biology , biochemistry
Aim To determine the effect of osteopontin (OPN) on autophagy and autophagy‐apoptosis interactions after SAH. Methods The endovascular perforation model of SAH or sham surgery was performed in a total of 86 Sprague‐Dawley male rats. The temporal expressions of endogenous OPN and autophagy‐related proteins (Beclin 1, ATG5, LC3 II to I ratio) were measured in sham and SAH rats at different time points (3, 6, 12, 24, and 72 hours). Rats were randomly divided into three groups: Sham, SAH + Vehicle (PBS, phosphate‐buffered saline), and SAH + rOPN (5 μg/rat recombinant OPN). Neurobehavioral tests were performed 24 hours after SAH, followed by the collection of brain samples for assessment of autophagy and apoptosis proteins. These tests assessed whether an autophagy‐apoptosis relationship existed on the histological level in the brain. Results Endogenous OPN and autophagy‐related proteins all increased after SAH. rOPN administration improved neurological dysfunction, increased the expression of autophagy‐related proteins (Beclin 1, ATG5, LC3 II to I ratio) and antiapoptotic protein Bcl‐2, while decreasing the expression of proapoptotic proteins (cleaved Caspase‐3 and Bax). rOPN also regulated autophagy‐apoptosis interactions 24 hours after SAH. Conclusion rOPN attenuates early brain injury and inhibits neuronal apoptosis by activating autophagy and regulating autophagy‐apoptosis interactions.