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

• Type of Material: Article
• Authors: Christy Joseph, University of Medicine, Greifswald; Ana-Maria Buga, University of Medicine, Greifswald; Raluca Vintilescu, University of Medicine, Greifswald; Adrian Tudor Balseanu, University of Medicine, Greifswald; Mihai Moldovan, University of Copenhagen; Heike Junker, Ernst-Moritz-Arndt-University; Lary Walker, Emory University; Martin Lotze, University of Greifswald; Aurel Popa-Wagner, University of Medicine Rostock
• Language: English
• Date: 2012-08
• Publisher: SAGE Publications
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2012, © SAGE Publications
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1038/jcbfm.2012.65
• Title of Journal or Parent Work: Journal of Cerebral Blood Flow and Metabolism
• ISSN: 0271-678X
• Volume: 32
• Issue: 8
• Start Page: 1632
• End Page: 1642
• Grant/Funding Information: This study was partially supported by a grant from the Ministry of Research and Education of Germany (FKZ 0314107) to APW.; MM was supported by a grant of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project No PN-II-ID-PCE-2011-3-0847.; A-MB was supported by a grant from ERA-NET FLARE2/UEFISCDI, project No 8555/2011.
• Keywords: EEG; aging; hypothermia; stroke; H2S; annexin A1
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

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 (H2S) 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 H2S-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 H2S. 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.