title: Delayed administration of the GLP-1 receptor agonist liraglutide improves metabolic and functional recovery after cerebral ischemia in rats.
abstract: Glucagon-like peptide 1 receptor (GLP-1R) agonists administered before or immediately after induction of experimental stroke have been shown to provide acute neuroprotection. Here, we determined whether delayed treatment with a GLP-1R agonist could improve metabolic and functional recovery after stroke. Rats were subjected to middle cerebral artery occlusion (MCAO) and given the well-established GLP-1R agonist liraglutide (50, 100, or 200μg/kg) or normal saline (NS) daily for 4 weeks, starting 1 day after MCAO. Cerebral glucose metabolism and neurological deficits were evaluated using18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging and modified neurological severity score (mNSS) test. Levels of neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), von Willebrand factor (vWF), and GLP-1R were assessed by immunohistochemical staining and Western blot analysis. PET imaging showed that animals treated with liraglutide had significantly higher18F-FDG accumulation in the cerebral infarction compared with animals treated with NS. Liraglutide significantly reduced the mNSS score. It also greatly increased the expression of NeuN, GFAP, vWF, and GLP-1R in the cerebral ischemic area at postoperative week 4. These results demonstrated metabolic and functional recovery after delayed treatment with liraglutide in a rat model of cerebral ischemia.
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, PR China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Dong
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, PR China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, PR China.
authors.forename: Aiying
authors.initials: A
authors.lastname: Chen
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, PR China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Fahuan
authors.initials: F
authors.lastname: Song
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, PR China; State Key Laboratory of Safety Evaluation for New Drugs, Zhejiang Academy of Medical Sciences, Hangzhou 310013, PR China. Electronic address: gaoli-z@163.com.
authors.forename: Gaoli
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D009478:Neuropeptide Y / Q000378:metabolism; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000255:Adenosine Triphosphate; D000069450:Liraglutide; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000626540:Tmem59 protein, mouse
keywords: Cerebral ischemia; Glucose metabolism; Liraglutide; Neurological function; Positron emission tomography