Efficacy of the lipid-soluble iron chelator 2,2'-dipyridyl against hemorrhagic brain injury

Neurobiol Dis. 2012 Jan;45(1):388-94. doi: 10.1016/j.nbd.2011.08.028. Epub 2011 Sep 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / pharmacology
  • 2,2'-Dipyridyl / therapeutic use*
  • Animals
  • Cell Death / drug effects
  • Chelating Agents / pharmacology
  • Chelating Agents / therapeutic use*
  • Intracranial Hemorrhages / drug therapy*
  • Intracranial Hemorrhages / metabolism
  • Intracranial Hemorrhages / pathology
  • Iron / metabolism*
  • Mice
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Treatment Outcome


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