Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons

Abstract

Glutamate is an important excitatory neurotransmitter in mammalian brains, but excessive amount of glutamate can cause “excitotoxicity” and lead to neuronal death. As bipolar neurons, spiral ganglion neurons (SGNs) function as a “bridge” in transmitting auditory information from the ear to the brain and can be damaged by excessive glutamate which results in sensorineural hearing loss. In this study, edaravone, a free radical scavenger, elicited both preventative and therapeutic effects on SGNs against glutamate-induced cell damage that was tested by MTT assay and trypan blue staining. Ho.33342 and PI double staining revealed that apoptosis as well as necrosis took place during glutamate treatment, and apoptosis was the main type of cell death. Oxidative stress played an important role in glutamate-induced cell damage but pretreatment with edaravone alleviated cell death. Results of western blot demonstrated that mechanisms underlying the toxicity of glutamate and the protection of edaravone were related to the PI3K pathway and Bcl-2 protein family.

Regulation of Noise-Induced Loss of Serotonin Transporters with Resveratrol in a Rat Model Using 4-[18F]-ADAM/Small-Animal Positron Emission Tomography

“…Hearing thresholds were temporally elevated and partially recovered later after noise exposure regardless of treatment with citalopram or resveratrol, which suggests that these drugs could not attenuate noise-induced hearing loss in the first phase of noise-induced glutamate excitotoxicity. In the second phase, glutamate excitotoxicity further causes spiral ganglion neuronal death primarily through the excessive activation of glutamate receptors, which triggers a massive Ca 2+ influx into neurons [38], resulting in the production of reactive oxygen species (ROS) and free radicals by mitochondria and, eventually, cell death [39]. Therefore, such changes of spiral ganglion cells are likely to alter the transmission of information in the ascending auditory pathway, and presumably contribute to the serotonergic neurotoxicity in the central nervous system.…”

Effects of Perinatal Fluoride Exposure on Short- and Long-Term Memory, Brain Antioxidant Status, and Glutamate Metabolism of Young Rat Pups

“…68,69 The association between neurotoxicity with oxidative stress and Glu excitotoxicity has been widely reported. 68,70,71 However, with the results obtained so far, it is difficult to propound a precise mechanism for F neurotoxicity. Other determinations, such as measurement of the levels of Glu in specific brain areas, or the activity of other Glu metabolism-related enzymes (besides GOT and GPT), would be necessary in order to complement the obtained data and to define if the glutamatergic system is involved.…”

Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review

“…Furthermore, GLT-1 is one of the most common transporters and consists of about 80% of the glutamate transporters expressed in the hippocampus (Mookherjee et al, 2011). There is also evolving evidence suggesting a blockade of certain Glu receptors and/ or enhancing the expression of GLT-1 shown to improve neurological outcomes in various experimental models of neurological illnesses (Zlotnik et al, 2008(Zlotnik et al, , 2009Wang et al, 2014;Bai et al, 2016). Among different agents tested, CEF is one of the betalactam antibiotics reported to have neuroprotective actions.…”