Osteopontin-Enhanced Autophagy Attenuates Early Brain Injury via FAK–ERK Pathway and Improves Long-Term Outcome after Subarachnoid Hemorrhage in Rats

Autor:	Lingyun Wu, Chengmei Sun, Budbazar Enkhjargal, Keren Zhou, Xiao-Dan Jiang, Qiquan Zhu, Jiping Tang, John H. Zhang, Zhiyi Xie, Cesar Reis, Tongyu Zhang
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	MAPK/ERK pathway Male autophagy Subarachnoid hemorrhage osteopontin subarachnoid hemorrhage delayed brain injury Pharmacology Hippocampal formation Article Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Western blot stomatognathic system medicine Animals Osteopontin cardiovascular diseases Extracellular Signal-Regulated MAP Kinases lcsh:QH301-705.5 030304 developmental biology 0303 health sciences medicine.diagnostic_test biology business.industry hippocampal injury Autophagy General Medicine medicine.disease Recombinant Proteins 3. Good health Rats nervous system diseases Disease Models Animal lcsh:Biology (General) Apoptosis Brain Injuries Focal Adhesion Protein-Tyrosine Kinases biology.protein Signal transduction business 030217 neurology & neurosurgery
Zdroj:	Cells, Vol 8, Iss 9, p 980 (2019) Cells Volume 8 Issue 9
ISSN:	2073-4409
Popis:	Osteopontin (OPN) enhances autophagy, reduces apoptosis, and attenuates early brain injury (EBI) after a subarachnoid hemorrhage (SAH). A total of 87 Sprague&ndash Dawley rats were subjected to sham or SAH operations to further investigate the signaling pathway involved in osteopontin-enhanced autophagy during EBI, and the potential effect of recombinant OPN (rOPN) administration to improve long-term outcomes after SAH. Rats were randomly divided into five groups: Sham, SAH + Vehicle (PBS, phosphate-buffered saline), SAH + rOPN (5 &mu g/rat recombinant OPN), SAH + rOPN + Fib-14 (30 mg/kg of focal adhesion kinase (FAK) inhibitor-14), and SAH + rOPN + DMSO (dimethyl sulfoxide). Short-term and long-term neurobehavior tests were performed, followed by a collection of brain samples for assessment of autophagy markers in neurons, pathway proteins expression, and delayed hippocampal injury. Western blot, double immunofluorescence staining, Nissl staining, and Fluoro-Jade C staining assay were used. Results showed that rOPN administration increased autophagy in neurons and improved neurobehavior in a rat model of SAH. With the administration of FAK inhibitor-14 (Fib-14), neurobehavioral improvement and autophagy enhancement induced by rOPN were abolished, and there were consistent changes in the phosphorylation level of ERK1/2. In addition, early administration of rOPN in rat SAH models improved long-term neurobehavior results, possibly by alleviating hippocampal injury. These results suggest that FAK&ndash ERK signaling may be involved in OPN-enhanced autophagy in the EBI phase after SAH. Early administration of rOPN may be a preventive and therapeutic strategy against delayed brain injury after SAH.
Databáze:	OpenAIRE
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