Background and purpose:
Intracerebral hemorrhage (ICH) is a devastating form of stroke with no clinically proven treatment. 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 ICH in middle-aged mice (12 months old).
Methods:
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.
Results:
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 (n=5 mice/group, all
p
<0.01). Post-treatment reduced brain lesion volume by 40.5%, lessened edema, and improved neurologic function (n=6-8 mice/group, all
p
<0.05) but did not affect body weight loss or mortality rate.
Conclusions:
The lipid-soluble ferrous iron chelator 2,2’-dipyridyl can reduce brain injury and improve functional recovery after ICH.
Corrigendum to “Ambroxol Improves Neuronal Survival and Reduces White Matter Damage through Suppressing Endoplasmic Reticulum Stress in Microglia after Intracerebral Hemorrhage”
