DOI: 10.14704/nq.2022.20.11.NQ66135

Excitotoxicity induced neuronal deterioration and an up-regulation of EAAT-2 expression via NF-kB pathway with Ceftriaxone: A Review

Gaddam Narasimha Rao, Srikanth Jupudi, Antony Justin

Abstract

Glutamate is the major excitatory amino acid in mammalian nervous system, it has the imperative role in signal transduction process. Oxygen glucose deprived condition like acute ischemic stroke and chronic neurodegenerative disorders such as Alzheimer’s, multiple sclerosis and amyotrophic lateral sclerosisare often enhances secretion of glutamate which eventually leads to excitotoxicity.Apart from the deficiency of energy metabolites, an ionic imbalance and ischemic reperfusion will causes oxidative stress followed by release of pro-inflammatory mediators likeTumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) and cytokine such as Inter leukin-1β (IL-1β) and Inter leukin -18 (IL-18). In generalastroglial cells uptake the glutamate through trans-membrane pumps called excitatory amino acid transporter-2 (EAAT-2) thereby it converts glutamate into harmless glutaminein normal physiology of brain.The expression of EAAT-2 protein on plasma membrane of astrocytes will be impaired during acute and chronic neurodegenerative disorders, up-regulation of EAAT-2 in unfavorable conditions like stroke and chronic neurodegenerative disorders could be helpful for neuroprotection. Recent studies revealed that Ceftriaxone can up-regulate EAAT-2 expression via NF-kB pathway. This review will brief the excitotoxicity induced neuronal deterioration, glutamate metabolism and mechanism ceftriaxone induced EAAT-2 expression.

Keywords

Glutamate, Excitotoxicity, ischemic stroke, Ceftriaxone, EAAT-2 expresion.

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