title: 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.
authors: Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
authors: Jayalakshmi
authors: J
authors: Caliaperumal
authors: Shannon
authors: S
authors: Wowk
authors: Sarah
authors: S
authors: Jones
authors: Yonglie
authors: Y
authors: Ma
authors: Frederick
authors: F
authors: Colbourne
mesh_terms: D015082:2,2'-Dipyridyl / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001519:Behavior / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy; D016022:Case-Control Studies; D016923:Cell Death / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D054022:Cerebrum / Q000187:drug effects*; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007501:Iron / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy*; D017211:Treatment Failure
chemical_list: D002614:Chelating Agents; D015082:2,2'-Dipyridyl; D007501:Iron