title: High-fat diet reduces neuroprotection of isoflurane post-treatment: Role of carboxyl-terminal modulator protein-Akt signaling.
abstract: OBJECTIVE
  High-fat diet (HFD) contributes to the increased prevalence of obesity and hyperlipidemia in young adults, a possible cause for their recent increase in stroke. Isoflurane post-treatment provides neuroprotection. Isoflurane post-treatment induced neuroprotection in HFD-fed mice was determined.
  
  
  METHODS
  Six-week old CD-1 male mice were fed HFD or regular diet (RD) for 5 or 10 weeks. Their hippocampal slices (400 µm) were subjected to oxygen-glucose deprivation (OGD). Some slices were exposed to isoflurane for 30 min immediately after OGD. Some mice had a 90-min middle cerebral arterial occlusion and were post-treated with 2% isoflurane for 30 min.
  
  
  RESULTS
  OGD time-dependently induced cell injury. This injury was dose-dependently reduced by isoflurane. The effect was apparent at 1% or 2% isoflurane in RD-fed mice but required 3% isoflurane in HFD-fed mice. HFD influenced the isoflurane effects in DG. OGD increased carboxyl-terminal modulator protein (CTMP), an Akt inhibitor, and decreased Akt signaling. Isoflurane reduced these effects. LY294002, an Akt activation inhibitor, attenuated the isoflurane effects. HFD increased CTMP and reduced Akt signaling. Isoflurane improved neurological outcome in the RD-fed mice but not in the HFD-fed mice.
  
  
  CONCLUSIONS
  HFD attenuated isoflurane post-treatment-induced neuroprotection possibly because of decreased prosurvival Akt signaling.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA; Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.forename: Jiao
authors.initials: J
authors.lastname: Deng
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D059305:Diet, High-Fat; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D010170:Palmitoyl-CoA Hydrolase; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D002867:Chromones; D009025:Morpholines; D018696:Neuroprotective Agents; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007530:Isoflurane; D051058:Oncogene Protein v-akt; C527670:CTMP protein, mouse; D010170:Palmitoyl-CoA Hydrolase; D005947:Glucose