title: Efficacy of the lipid-soluble iron chelator 2,2'-dipyridyl against hemorrhagic brain injury.
abstract: Previous studies have indicated that 2,2'-dipyridyl, a lipid-soluble ferrous iron chelator, can reduce brain injury after cerebral ischemia and reduce cerebral vasospasm after subarachnoid hemorrhage. In this study, we examined the efficacy of 2,2'-dipyridyl after intracerebral hemorrhage (ICH) in 12-month-old mice. ICH was modeled by intrastriatal injection of collagenase or autologous whole blood. 2,2'-Dipyridyl or vehicle was administered intraperitoneally 2h before ICH (pretreatment) or 6h after ICH (post-treatment) and then once daily for up to 3 days. Mice in the pretreatment group were sacrificed 1 or 3 days after ICH and examined for iron deposition, neuronal death, oxidative stress, microglial/astrocyte activation, neutrophil infiltration, and white matter damage. Mice in the post-treatment group were examined for brain lesion volume and edema on day 3 and for neurologic deficits on days 1, 3, and 28 after ICH. Pretreatment with 2,2'-dipyridyl decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, reduced microglial activation without affecting astrocytes or neutrophil infiltration, and attenuated white matter damage. Post-treatment reduced brain lesion volume and edema and improved neurologic function. These results indicate that the lipid-soluble ferrous iron chelator 2,2'-dipyridyl can reduce brain injury and improve functional outcome after ICH.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
authors.forename: He
authors.initials: H
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Mingchang
authors.initials: M
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D015082:2,2'-Dipyridyl / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020300:Intracranial Hemorrhages / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D002614:Chelating Agents; D015082:2,2'-Dipyridyl; D007501:Iron