Edaravone attenuates H < sub > 2 < /sub > O < sub > 2 < /sub > or glutamate-induced toxicity in hippocampal neurons and improves AlCl < sub > 3 < /sub > /D-galactose induced cognitive impairment in mice

Neurotoxicology. 2021 May 15;85:68-78. doi: 10.1016/j.neuro.2021.05.005. Online ahead of print.ABSTRACTEdaravone (Eda) is a free radical scavenger used in clinical trials for the treatment of ischemic stroke and amyotrophic lateral sclerosis. However, how Eda exerts its neuroprotective effects remains to be elucidated. We investigated the neuroprotective effects of Eda in cultured hippocampal neurons and in a mouse model of AlCl3/D-galactose-induced cognitive impairment. Eda protected hippocampal neurons by eliminating H2O2 or glutamate-induced toxicity, leading to decreased cell viability and neurite shortening. Consistently, Eda restored impaired levels of BDNF, FGF2 and their associated signaling axes (including TrkB, p-Akt and Bcl-2) to attenuate neuronal death. In a mouse model of chemically-induced cognitive impairment, Eda restored the levels of BDNF, FGF2 and TrkB/Akt signaling axis to attenuate neuronal apoptosis, thereby ameliorating cognitive impairment. Meanwhile, the pro-inflammation was eliminated due to the restoration of pro-inflammatory factors such as TNF-α, IL-6, IL-1β, and NOS2. In summary, Eda is an effective drug for protecting neurons from neurotoxic injury. BDNF, FGF2, and their regulated pathways may be potential therapeutic targets for neuroprotection.PMID:34004234 | DOI:10.1016/j.neuro.2021.05.005
Source: Neurotoxicology - Category: Neurology Authors: Source Type: research