Bipyridine, an Iron Chelator, Does Not Lessen Intracerebral Iron-Induced Damage or Improve Outcome After Intracerebral H
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ORIGINAL ARTICLE
Bipyridine, an Iron Chelator, Does Not Lessen Intracerebral Iron-Induced Damage or Improve Outcome After Intracerebral Hemorrhagic Stroke in Rats Jayalakshmi Caliaperumal & Shannon Wowk & Sarah Jones & Yonglie Ma & Frederick Colbourne Received: 20 December 2012 / Revised: 18 July 2013 / Accepted: 19 July 2013 / Published online: 6 August 2013 # Springer Science+Business Media New York 2013
Abstract Iron chelators, such as the intracellular ferrous chelator 2,2′-bipyridine, are a potential means of ameliorating ironinduced injury after intracerebral hemorrhage (ICH). We evaluated bipyridine against the collagenase and whole-blood ICH models and a simplified model of iron-induced damage involving a striatal injection of FeCl2 in adult rats. First, we assessed whether bipyridine (25 mg/kg beginning 12 h post-ICH and every 12 h for 3 days) would attenuate non-heme iron levels in the brain and lessen behavioral impairments (neurological deficit scale, corner turn test, and horizontal ladder) 7 days after collagenase-induced ICH. Second, we evaluated bipyridine (20 mg/kg beginning 6 h post-ICH and then every 24 h) on edema 3 days after collagenase infusion. Body temperature was continually recorded in a subset of these rats beginning 24 h prior to ICH until euthanasia. Third, bipyridine was administered (as per experiment 2) after whole-blood infusion to examine tissue loss, neuronal degeneration, and behavioral impairments at 7 days post-stroke, as well as body temperature for 3 days post-stroke. Finally, we evaluated whether bipyridine (25 mg/kg given 2 h prior to surgery and then every 12 h for 3 days) lessens tissue loss, neuronal death, and behavioral deficits after striatal FeCl2 injection. Bipyridine caused a significant hypothermic effect (maximum drop to 34.6 °C for 2– 5 h after each injection) in both ICH models; however, in all experiments bipyridine-treated rats were indistinguishable
Jayalakshmi Caliaperumal and Shannon Wowk contributed equally J. Caliaperumal : S. Wowk : F. Colbourne Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada S. Jones : Y. Ma : F. Colbourne (*) Department of Psychology, Biological Sciences, University of Alberta, Room P217 Biological Sciences Building, Edmonton T6G 2E9, Alberta, Canada e-mail: [email protected] URL: http://www.psych.ualberta.ca/~fcolbour/Fred_Colbourne/ Home.html
from vehicle controls on all other measures (e.g., tissue loss, behavioral impairments, etc.). These results do not support the use of bipyridine against ICH. Keywords Intracerebral hemorrhage . Bipyridine . Iron toxicity . Iron chelater . Hypothermia . Stroke Abbreviations ICH Bipyridine BIP SAL NDS CTT BWC Cb
Intracerebral hemorrhage 2,2′-Bipyridine Bipyridine group Saline group Neurological deficit scale Corner turn test Brain water content Cerebellum
Introduction Intracerebral hemorrhage (ICH) has a high mortality rate and greatly impairs survivors [1]. Currently, no clinically approved neuroprotective treatments exist. The primary damage of an ICH (i.e., m
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