Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4351712 | Neuroscience Research | 2009 | 6 Pages |
Abstract
Iron accumulates in the brain and contributes to brain injury after intracerebral hemorrhage (ICH). The c-Jun-N-terminal kinase (JNK) signaling pathway mediates cell death after ischemic stroke, however, the involvement of JNK in ICH is not well known. This study investigated whether the JNK signaling pathway is activated by iron after ICH. Male Sprague-Dawley rats received an infusion of autologous whole blood (as a model of ICH) or ferrous iron into the right basal ganglia and control rats had an infusion of saline. Some ICH rats were treated with either deferoxamine (DFX), an iron chelator, or vehicle. Activation of JNK was measured by Western blot analysis and immunohistochemistry. Free iron in cerebrospinal fluid (CSF) and behavioral outcomes following ICH were also examined. We found that activated JNK in the brain were increased after ICH, and an intracerebral infusion of ferrous iron also upregulated brain activated JNK. Free iron accumulated in CSF and systemic administration of DFX after ICH reduces free iron contents in CSF, suppresses JNK activation and improves ICH-induced neurological deficits. Our results demonstrated that the JNK signaling pathway is activated after ICH and iron may contribute to this activation. DFX reduces free iron levels and attenuates activation of JNK suggesting iron chelation may be useful therapy for ICH patients.
Keywords
PBSpower of hydrogenFDAc-Jun-N-terminal kinasePaO2DFXPaCO2ECLi.p.kiloDaltonkDaDeferoxamineJnkIgGSDS–PAGEadenosine triphosphataseIronsodium dodecyl sulfate–polyacrylamide gel electrophoresisimmunoglobulin GATPaseenhanced chemiluminescenceintraperitoneal injectionintracerebral hemorrhageCerebral hemorrhageFood and Drug AdministrationCerebrospinal fluidCSFPhosphate-buffered salineICHHolo-transferrin
Related Topics
Life Sciences
Neuroscience
Neuroscience (General)
Authors
Shu Wan, Renya Zhan, Shusen Zheng, Ya Hua, Guohua Xi,