title: Trans-sodium crocetinate provides neuroprotection against cerebral ischemia and reperfusion in obese mice.
abstract: Trans-sodium crocetinate (TSC) is a novel synthetic carotenoid compound that improves diffusion of small molecules, including oxygen, in solutions. TSC provides neuroprotection in healthy rats and rabbits. This study seeks to determine whether TSC is neuroprotective in obese mice. Sixteen-week-old CD-1 male mice that had been fed a high-fat diet for 10 weeks were subjected to a 90-min middle cerebral arterial occlusion (MCAO). They received TSC by two boluses through a tail vein 10 min after the onset of MCAO and reperfusion, respectively, with doses of 0.14, 0.28, and 0.7 mg/kg or by a bolus-infusion-bolus strategy with a dose of 0.14 mg/kg during MCAO. The neurological outcome was evaluated 72 hr after MCAO. Brain tissues were harvested 24 hr after MCAO to measure nitrotyrosine-containing proteins, 4-hydroxy-2-nonenal, matrix metalloproteinase (MMP)-2 and -9 activity and expression, and inflammatory cytokines. TSC given in the two-bolus strategy did not improve the neurological outcome. The bolus-infusion-bolus strategy significantly reduced brain edema, infarct volume, and hemorrhagic transformation and improved neurological functions. TSC reduced nitrotyrosine-containing proteins, MMP-9 activity and expression, and inflammatory cytokines in ischemic brain tissues. Our results indicate that TSC delivered by the bolus-infusion-bolus strategy provides neuroprotection in obese mice. This protection may occur through reduction of oxidative stress, MMP-9 activity, or inflammatory cytokines in the ischemic brain tissues.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, Virginia; Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Deng
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy; D002338:Carotenoids; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009765:Obesity; D018384:Oxidative Stress / Q000187:drug effects; D015424:Reperfusion; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000447:Aldehydes; D016207:Cytokines; D018696:Neuroprotective Agents; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; C002744:3-nitrotyrosine; D014443:Tyrosine; D020782:Matrix Metalloproteinases; C027576:4-hydroxy-2-nonenal
keywords: focal brain ischemia; hemorrhagic transformation; matrix metalloproteinase-9; neuroprotection; obesity; trans-sodium crocetinate