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

Transl Stroke Res. 2013 Dec;4(6):719-28. doi: 10.1007/s12975-013-0272-3. Epub 2013 Aug 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / administration & dosage
  • 2,2'-Dipyridyl / 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
  • Chelating Agents / 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

Substances

  • Chelating Agents
  • 2,2'-Dipyridyl
  • Iron