title: Obesity and hyperglycemia lead to impaired post-ischemic recovery after permanent ischemia in mice.
abstract: OBJECTIVE
  Obesity-induced diabetes has increased over the years and has become one of the risk factors for stroke. We investigated the influence of diet-induced obesity and hyperglycemia on permanent distal middle cerebral artery occlusion (pMCAO)-induced ischemic stroke in mice.
  
  
  METHODS
  Male C57/Bl6 mice were treated with a high-fat/high-carbohydrate diet [HFCD/obese and hyperglycemia (O/H)] or a normal diet (control) for 3.5 months, subjected to pMCAO, and sacrificed after 7 days.
  
  
  RESULTS
  Infarct volume analysis showed no differences between the O/H and control group, whereas neurological deficits were significantly higher in the O/H group compared to the control group. Sirtuin (Sirt1) was overexpressed and NADPH oxidase was reduced in the O/H group. O/H mice had significantly lower expression of Wnt and glycogen synthase kinase 3 α and β, a key component in the Wnt signaling pathway. Translocation of apoptosis inducing factor (AIF) to the nucleus was observed in both the O/H and control groups, but O/H mice showed a higher expression of AIF in the nucleus.
  
  
  CONCLUSIONS
  These data suggest that impaired Wnt signaling and active apoptosis result in reduced post-stroke recovery in obese and hyperglycemic mice.
authors.affiliation: Department of Medicinal and Biological Chemistry, University of Toledo, Toledo, Ohio, USA.
authors.forename: Jatin
authors.initials: J
authors.lastname: Tulsulkar
authors.affiliation: Department of Medicinal and Biological Chemistry, University of Toledo, Toledo, Ohio, USA.
authors.forename: Shadia E
authors.initials: SE
authors.lastname: Nada
authors.affiliation: Department of Medicinal and Biological Chemistry, University of Toledo, Toledo, Ohio, USA.
authors.forename: Brandon D
authors.initials: BD
authors.lastname: Slotterbeck
authors.affiliation: Department of Medicinal and Biological Chemistry, University of Toledo, Toledo, Ohio, USA.|Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, Ohio, USA.|Center for Diabetes and Endocrine Research (CeDER), University of Toledo, Toledo, Ohio, USA.
authors.forename: Marcia F
authors.initials: MF
authors.lastname: McInerney
authors.affiliation: Department of Medicinal and Biological Chemistry, University of Toledo, Toledo, Ohio, USA.|Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, Ohio, USA.
authors.forename: Zahoor A
authors.initials: ZA
authors.lastname: Shah
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3; D006943:Hyperglycemia / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha