Edaravone injection ameliorates cognitive deficits in rat model of Alzheimer’s disease

Abstract

Oxidative stress plays important role in the pathogenesis of Alzheimer's disease (AD). Edaravone is a potent free radical scavenger that exerts antioxidant effects. Therefore, in this study we aimed to investigate neuroprotective effects of edaravone for AD. Wistar rats were randomly divided into three groups (n = 15): control group, model group, and treatment group, which were injected with phosphate buffered saline, Aβ1-40, and Aβ1-40 together with 5 mg/kg edaravone, respectively, into the right hippocampal dentate gyrus. Spatial learning and memory of the rats were examined by Morris water maze test. 4-Hydroxynonenal (4-HNE) level in rat hippocampus was analyzed by immunohistochemistry. Acetylcholinesterase (AChE) and choline acetylase (ChAT) activities were assayed by commercial kits. We found that edaravone ameliorated spatial learning and memory deficits in the rats. 4-HNE level in the hippocampus as well as AChE and ChAT activities in the hippocampus was significantly lower in treatment group than in model group. In conclusion, edaravone may be developed as a novel agent for the treatment of AD for improving cholinergic system and protecting neurons from oxidative toxicity.

Clinical and Pathological Benefits of Edaravone for Alzheimer’s Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model

“…ROS is one of the crucial factors promoting the pathological progression of AD via aggregating the toxicity of Aβ and CCH-driven vicious cycles [23,24]. Previous studies showed that EDA not only had inhibition effects on multiple key AD pathways including Aβ, Tau-hyperphosphorylation, neuroinflammation, neural oxidative stress, and neuronal loss via scavenging both ROS and Aβ in a family AD mouse model [25] but also alleviated Aβ or streptozotocin-induced cognitive impairment via anti-oxidative stress and anti-inflammationin in rat models [26,27] or in invitro models [28,29]. Moreover, recent experimental studies also found that EDA could attenuate cognitive deficits via inhibiting oxidative stress induced by CCH in rat models [18,30].…”

Nanotherapy for Alzheimer's disease and vascular dementia: Targeting senile endothelium

“…Lastly, this documented ability of LCM/ND lipid nanoemulsion to function as a carrier of selected small molecular compounds would, of course, be potentially applicable to certain drug molecules already being used in research for treating Alzheimer's disease (and brain injury). Several low-molecular-weight, and sufficiently lipophilic, candidates for incorporation into the LCM/ND lipid nanoemulsion are Edaravone (Jiao et al 2015;Yang et al 2015), caffeine (Chen et al 2010;Chieffi et al 2011;Marques et al 2011;Mohan et al 2015), resveratrol (Turner et al 2015;Zhao et al 2015), and docosahexaenoic acid or DHA Hashimoto et al 2016;Hjorth et al 2013;Mayurasakorn et al 2016;Pan et al 2015;Vandal et al 2014;Williams et al 2013;Yassine et al 2016aYassine et al , 2016b.…”

Advances in clinical neurology through the journal “Neurological Sciences” (2015–2016)

“…Edaravone, a potent free radical scavenger with antioxidant effects, may be developed as a novel agent for the treatment of AD for improving cholinergic system and protecting neurons from oxidative toxicity [110]. The mammalian target of rapamycin (mTOR) pathway has been reported to mediate Ab clearance through autophagy and may represent an important therapeutic target for AD [111].…”