Exendin-4 Inhibits Matrix Metalloproteinase-9 Activation and Reduces Infarct Growth After Focal Cerebral Ischemia in Hyperglycemic Mice

BACKGROUND AND PURPOSE—Admission hyperglycemia is an independent risk factor for poor outcome of ischemic stroke. Amelioration of hyperglycemia by insulin has not been shown to improve the poststroke outcome. Glucagon-like peptide 1 receptor agonists, which modulate glucose levels by stimulating ins...

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Bibliographic Details
Published in:Stroke (1970) 2016-05, Vol.47 (5), p.1328-1335
Main Authors: Kuroki, Takuma, Tanaka, Ryota, Shimada, Yoshiaki, Yamashiro, Kazuo, Ueno, Yuji, Shimura, Hideki, Urabe, Takao, Hattori, Nobutaka
Format: Article
Language:English
Subjects:
Animals
Blood-Brain Barrier - drug effects
Brain Ischemia - drug therapy
Brain Ischemia - pathology
Disease Models, Animal
Hyperglycemia - drug therapy
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - pharmacology
Infarction, Middle Cerebral Artery - drug therapy
Infarction, Middle Cerebral Artery - pathology
Male
Matrix Metalloproteinase 9 - drug effects
Mice, Inbred C57BL
Peptides - administration & dosage
Peptides - pharmacology
Venoms - administration & dosage
Venoms - pharmacology
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Summary:BACKGROUND AND PURPOSE—Admission hyperglycemia is an independent risk factor for poor outcome of ischemic stroke. Amelioration of hyperglycemia by insulin has not been shown to improve the poststroke outcome. Glucagon-like peptide 1 receptor agonists, which modulate glucose levels by stimulating insulin secretion, have been shown to exert cytoprotective effects by inhibiting inflammation and oxidative stress. This study aimed to evaluate whether the glucagon-like peptide 1 receptor agonist exendin-4 could reduce glucose levels and exert protective effects after acute focal ischemia in hyperglycemic mice. METHODS—Hyperglycemia was induced by intraperitoneal injection of dextrose 15 minutes before transient middle cerebral artery occlusion was performed for 60 minutes using an intraluminal thread. We assessed 4 groups(1) normal glucose (vehicle control), (2) induced hyperglycemia, (3) induced hyperglycemia with insulin treatment, and (4) induced hyperglycemia with exendin-4 treatment. Neurovascular injuries in brains from each group were evaluated 24 hours and 7 days post ischemia. RESULTS—Hyperglycemia significantly increased infarct volume (36.3±1.20 versus 26.9±1.28; P
ISSN:0039-2499
1524-4628
DOI:10.1161/STROKEAHA.116.012934