TY - JOUR
T1 - Efficacy of the lipid-soluble iron chelator 2,2'-dipyridyl against hemorrhagic brain injury
AU - Wu, He
AU - Wu, Tao
AU - Li, Mingchang
AU - Wang, Jian
N1 - Funding Information:
This work was supported by AHA 09BGIA2080137 and NIH K01AG031926 (JW). We thank Sarah Busse and Jessica Wang for blind analysis of histology and immunofluorescence, Dr. Raymond C. Koehler for valuable suggestions and comments, and Claire Levine for assistance with manuscript preparation.
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - 2,2'-dipyridyl
KW - Intracerebral hemorrhage
KW - Iron
KW - Neuronal death
KW - White matter
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U2 - 10.1016/j.nbd.2011.08.028
DO - 10.1016/j.nbd.2011.08.028
M3 - Article
C2 - 21930208
AN - SCOPUS:81955160700
SN - 0969-9961
VL - 45
SP - 388
EP - 394
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -