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  • Title: Edaravone Reduces Iron-Mediated Hydrocephalus and Behavioral Disorder in Rat by Activating the Nrf2/HO-1 Pathway.
    Author: Zhang J, Shi X, Chen Z, Geng J, Wang Y, Feng H, Zhu G, Chen Q.
    Journal: J Stroke Cerebrovasc Dis; 2018 Dec; 27(12):3511-3520. PubMed ID: 30205995.
    Abstract:
    Our previous studies have demonstrated that hemorrhage-derived iron has a key role in causing brain injury after intraventricular hemorrhage (IVH). Based on this finding, we hypothesized that edaravone, a free-radical scavenger, has the potential to alleviate hydrocephalus and neurological deficits post-IVH by suppressing iron-induced oxidative stress. Thus, this study aimed to investigate the efficacy of edaravone for rats with FeCl3 injection, as well as to explore the related molecular mechanism. An experimental model was established in adult male Sprague-Dawley rats via FeCl3 injection into the right lateral ventricle. Edaravone or vehicle was administered immediately, 1 day and 2 days after intraventricular injection. Brain water content, magnetic resonance imaging, neurological score, oxidative stress assays, Western blot analysis, and electron microscopy were employed to evaluate brain injury in these rats. Intraventricular injection of FeCl3 induced brain edema, ventricular dilation, and neurobehavioral disorder in rats. Edaravone treatment significantly attenuated the above symptoms, reduced ependymal cilia and neuron damage, and inhibited oxidative stress (elevated levels of an antioxidant, superoxide dismutase; decreased levels of an oxidant, malondialdehyde). Moreover, edaravone administration effectively activated the Nrf2/HO-1 signaling pathway in rat brain following FeCl3 injection. These results showed that edaravone treatment alleviated brain edema, ventricular expansion, and neurological disorder after FeCl3 injection. The possible mechanism is by protecting ependymal cilia and neurons from oxidative stress injury and activating the Nrf2/HO-1 signaling pathway. These results provide further experimental evidence for edaravone application in the treatment of IVH.
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