Kainic Acid-Induced Neurotoxicity: Targeting Glial Responses and Glia-Derived Cytokines

Author(s): Xing-Mei Zhang, Jie Zhu.

Journal Name: Current Neuropharmacology

Volume 9 , Issue 2 , 2011

Submit Manuscript
Submit Proposal

Abstract:

Glutamate excitotoxicity contributes to a variety of disorders in the central nervous system, which is triggered primarily by excessive Ca2+ influx arising from overstimulation of glutamate receptors, followed by disintegration of the endoplasmic reticulum (ER) membrane and ER stress, the generation and detoxification of reactive oxygen species as well as mitochondrial dysfunction, leading to neuronal apoptosis and necrosis. Kainic acid (KA), a potent agonist to the α-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate class of glutamate receptors, is 30-fold more potent in neurotoxicity than glutamate. In rodents, KA injection resulted in recurrent seizures, behavioral changes and subsequent degeneration of selective populations of neurons in the brain, which has been widely used as a model to study the mechanisms of neurodegenerative pathways induced by excitatory neurotransmitter. Microglial activation and astrocytes proliferation are the other characteristics of KA-induced neurodegeneration. The cytokines and other inflammatory molecules secreted by activated glia cells can modify the outcome of disease progression. Thus, anti-oxidant and anti-inflammatory treatment could attenuate or prevent KA-induced neurodegeneration. In this review, we summarized updated experimental data with regard to the KA-induced neurotoxicity in the brain and emphasized glial responses and glia-oriented cytokines, tumor necrosis factor-α, interleukin (IL)-1, IL-12 and IL-18.

Keywords: Kainic acid, excitotoxicity, microglia, astrocytes, cytokines, glutamate receptors, mitochondrial function, ionotropic gluatamate, kainate receptors

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 9
ISSUE: 2
Year: 2011
Page: [388 - 398]
Pages: 11
DOI: 10.2174/157015911795596540
Price: $58

Article Metrics

PDF: 10