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Bipyridine, an iron chelator, does not lessen intracerebral iron-induced damage or improve outcome after intracerebral hemorrhagic stroke in rats.

Abstract
Iron chelators, such as the intracellular ferrous chelator 2,2'-bipyridine, are a potential means of ameliorating iron-induced 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 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.
AuthorsJayalakshmi Caliaperumal, Shannon Wowk, Sarah Jones, Yonglie Ma, Frederick Colbourne
JournalTranslational stroke research (Transl Stroke Res) Vol. 4 Issue 6 Pg. 719-28 (Dec 2013) ISSN: 1868-601X [Electronic] United States
PMID24323426 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chelating Agents
  • 2,2'-Dipyridyl
  • Iron
Topics
  • 2,2'-Dipyridyl (administration & dosage, pharmacology)
  • Animals
  • Behavior (drug effects)
  • Body Temperature (drug effects)
  • Brain Edema (drug therapy)
  • Case-Control Studies
  • Cell Death (drug effects)
  • Cerebral Hemorrhage (drug therapy)
  • Cerebrum (drug effects)
  • Chelating Agents (administration & dosage, pharmacology)
  • Disease Models, Animal
  • Drug Evaluation, Preclinical (methods)
  • Iron (metabolism)
  • Male
  • Nerve Degeneration (drug therapy)
  • Neurons (drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Stroke (drug therapy)
  • Treatment Failure

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