title: Trefoil factor 3 as an endocrine neuroprotective factor from the liver in experimental cerebral ischemia/reperfusion injury.
abstract: Cerebral ischemia, while causing neuronal injury, can activate innate neuroprotective mechanisms, minimizing neuronal death. In this report, we demonstrate that experimental cerebral ischemia/reperfusion injury in the mouse causes upregulation of the secretory protein trefoil factor 3 (TFF3) in the hepatocyte in association with an increase in serum TFF3. Partial hepatectomy (~60% liver resection) immediately following cerebral injury significantly lowered the serum level of TFF3, suggesting a contribution of the liver to the elevation of serum TFF3. Compared to wild-type mice, TFF3(-/-) mice exhibited a significantly higher activity of caspase 3 and level of cell death in the ischemic cerebral lesion, a larger fraction of cerebral infarcts, and a smaller fraction of the injured cerebral hemisphere, accompanied by severer forelimb motor deficits. Intravenous administration of recombinant TFF3 reversed changes in cerebral injury and forelimb motor function due to TFF3 deficiency. These observations suggest an endocrine neuroprotective mechanism involving TFF3 from the liver in experimental cerebral ischemia/reperfusion injury.
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Shu Q
authors.initials: SQ
authors.lastname: Liu
authors.forename: Derek
authors.initials: D
authors.lastname: Roberts
authors.forename: Brian
authors.initials: B
authors.lastname: Zhang
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Ren
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Zhang
authors.forename: Yu H
authors.initials: YH
authors.lastname: Wu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009077:Mucins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D000071165:Trefoil Factor-3; D015854:Up-Regulation / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009077:Mucins; D018696:Neuroprotective Agents; C493263:Tff3 protein, mouse; D000071165:Trefoil Factor-3; D053148:Caspase 3