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

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 1...

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Bibliographic Details
Main Authors: He Wu, Tao Wu, Mingchang Li, Jian Wang
Format: Article
Language:English
Published: Elsevier 2012-01-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996111002944
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Summary: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 2 h before ICH (pretreatment) or 6 h 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.
ISSN:1095-953X