title: Cardiac Arrest Alters Regional Ubiquitin Levels in Association with the Blood-Brain Barrier Breakdown and Neuronal Damages in the Porcine Brain.
abstract: The possibility that ubiquitin expression is altered in cardiac arrest-associated neuropathology was examined in a porcine model using immunohistochemical and biochemical methods. Our observations show that cardiac arrest induces progressive increase in ubiquitin expression in the cortex and hippocampus in a selective and specific manner as compared to corresponding control brains using enzyme-linked immunoassay technique (enzyme-linked immunosorbent assay (ELISA)). Furthermore, immunohistochemical studies showed ubiquitin expression in the neurons exhibiting immunoreaction in the cytoplasm and karyoplasm of distorted or damaged cells. Separate Nissl and ubiquitin staining showed damaged and distorted neurons and in the same cortical region ubiquitin expression indicating that ubiquitin expression after cardiac arrest represents dying neurons. The finding that methylene blue treatment markedly induced neuroprotection following identical cardiac arrest and reduced ubiquitin expression strengthens this view. Taken together, our observations are the first to show that cardiac arrest enhanced ubiquitin expression in the brain that is related to the magnitude of neuronal injury and the finding that methylene blue reduced ubiquitin expression points to its role in cell damage, not reported earlier.
authors.affiliation: Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University, S-75185, Uppsala, Sweden, Sharma@surgsci.uu.se.
authors.forename: Hari S
authors.initials: HS
authors.lastname: Sharma
authors.forename: Ranjana
authors.initials: R
authors.lastname: Patnaik
authors.forename: Aruna
authors.initials: A
authors.lastname: Sharma
authors.forename: José Vicente
authors.initials: JV
authors.lastname: Lafuente
authors.forename: Adriana
authors.initials: A
authors.lastname: Miclescu
authors.forename: Lars
authors.initials: L
authors.lastname: Wiklund
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D016887:Cardiopulmonary Resuscitation; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D006323:Heart Arrest / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008751:Methylene Blue / Q000494:pharmacology / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011897:Random Allocation; D012709:Serum Albumin / Q000032:analysis; D034421:Sus scrofa; D013552:Swine; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D025801:Ubiquitin / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D009419:Nerve Tissue Proteins; D012709:Serum Albumin; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D008751:Methylene Blue