title: Iron mediates endothelial cell damage and blood-brain barrier opening in the hippocampus after transient forebrain ischemia in rats.
abstract: Blood cells are transported into the brain and are thought to participate in neurodegenerative processes following hypoxic ischemic injury. We examined the possibility that transient forebrain ischemia (TFI) causes the blood-brain barrier (BBB) to become permeable to blood cells, possibly via dysfunction and degeneration of endothelial cells in rats. Extravasation of Evans blue and immunoglobulin G (IgG) was observed in the hippocampal CA1-2 areas within 8 h after TFI, and peaked at 48 h. This extravasation was accompanied by loss of tight junction proteins, occludin, and zonula occludens-1, and degeneration of endothelial cells in the CA1-2 areas. Iron overload and mitochondrial free radical production were evident in the microvessel endothelium of the hippocampus before endothelial cell damage occurred. Administration of deferoxamine (DFO), an iron chelator, or Neu2000, an antioxidant, blocked free radical production and endothelial cell degeneration. Our findings suggest that iron overload and iron-mediated free radical production cause loss of tight junction proteins and degeneration of endothelial cells, opening of the BBB after TFI.
authors.affiliation: Neuroscience Graduate Program, Brain Disease Research Center, Institute for Medical Science, Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Won
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Ui Jin
authors.initials: UJ
authors.lastname: Park
authors.forename: Jina
authors.initials: J
authors.lastname: Gwag
authors.forename: Byoung Joo
authors.initials: BJ
authors.lastname: Gwag
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Lee
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000378:metabolism*; D005070:Evans Blue / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005609:Free Radicals; D008565:Membrane Proteins; D005070:Evans Blue; D007501:Iron