Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats

Experimental Neurology
Wei NiYa Hua

Abstract

Iron contributes to c-Jun N-terminal kinases (JNK) activation in young rats and white matter injury in piglets after intracerebral hemorrhage (ICH). In the present study, we examined the effect of deferoxamine on ICH-induced white matter injury and JNK activation and in aged rats. Male Fischer 344 rats (18months old) had either an intracaudate injection of 100μl of autologous blood or a needle insertion (sham). The rats were treated with deferoxamine or vehicle with different regimen (dosage, duration and time window). White matter injury and activation of JNK were examined. We found that a dose of DFX should be at more than 10mg/kg for a therapeutic duration more than 2days with a therapeutic time window of 12h to reduce ICH-induced white matter loss at 2months. ICH-induced white matter injury was associated with JNK activation. The protein levels of phosphorylated-JNK (P-JNK) were upregulated at day-1 after ICH and then gradually decreased. P-JNK immunoreactivity was mostly located in white matter bundles. ICH-induced JNK activation was reduced by DFX treatment. This study demonstrated that DFX can reduce ICH-induced JNK activation and white matter damage.

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Citations

Feb 19, 2016·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Chuanyuan TaoChao You
Jun 16, 2015·Translational Stroke Research·Frieder Schlunk, Steven M Greenberg
Sep 14, 2016·Journal of Neuroinflammation·Robert H LeBlancKhalid A Hanafy
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Sep 27, 2019·CNS Neuroscience & Therapeutics·Heng YangYu-Xiang Gu
Sep 12, 2017·Frontiers in Human Neuroscience·Chuanyuan TaoChao You
Jul 25, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Heng YangYuxiang Gu
Jul 7, 2017·BioMed Research International·Shilun ZuoHua Feng
Sep 13, 2018·Translational Stroke Research·Xiang LiGang Chen
Dec 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jing XuGang Chen
Jun 29, 2021·Frontiers in Neurology·Xiongjie FuGao Chen

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