title: Prolonged gaseous hypothermia prevents the upregulation of phagocytosis-specific protein annexin 1 and causes low-amplitude EEG activity in the aged rat brain after cerebral ischemia.
abstract: In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. In animal studies of focal ischemia, short-term hypothermia often reduces infarct size. Nevertheless, efficient neuroprotection requires long-term, regulated lowering of whole-body temperature. Previously, we reported that post-stroke exposure to hydrogen sulfide (H(2)S) effectively lowers whole-body temperature and confers neuroprotection in aged animals. In the present study using magnetic resonance imaging, electroencephalogram recording, DNA arrays, reverse transcriptase polymerase chain reaction, western blotting and immunofluorescence, we characterized the central nervous system response to H(2)S-induced hypothermia and report, for the first time, that annexin A1, a major pro-inflammatory protein that is upregulated after stroke, was consistently downregulated in polymorphonuclear cells in the peri-lesional cortex of post-ischemic, aged rat brain after 48 hours of hypothermia induced by exposure to H(2)S. Our data suggest that long-term hypothermia may be a viable clinical approach to protecting the aged brain from cerebral injury. Our findings further suggest that, in contrast to monotherapies that have thus far uniformly failed in clinical practice, hypothermia has pleiotropic effects on brain physiology that may be necessary for effective protection of the brain after stroke.
authors.affiliation: Molecular Neurobiology Laboratory, Clinic of Neurology, University of Medicine, Greifswald, Germany.
authors.forename: Christy
authors.initials: C
authors.lastname: Joseph
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Buga
authors.forename: Raluca
authors.initials: R
authors.lastname: Vintilescu
authors.forename: Adrian Tudor
authors.initials: AT
authors.lastname: Balseanu
authors.forename: Mihai
authors.initials: M
authors.lastname: Moldovan
authors.forename: Heike
authors.initials: H
authors.lastname: Junker
authors.forename: Lary
authors.initials: L
authors.lastname: Walker
authors.forename: Martin
authors.initials: M
authors.lastname: Lotze
authors.forename: Aurel
authors.initials: A
authors.lastname: Popa-Wagner
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D017305:Annexin A1 / Q000096:biosynthesis*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004569:Electroencephalography; D015180:Electrophoresis, Gel, Two-Dimensional; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D007036:Hypothermia, Induced / Q000379:methods*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000502:physiology*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013686:Telemetry; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D017305:Annexin A1; D012313:RNA; D006862:Hydrogen Sulfide