Glutamate excitotoxicity contributes to a variety of disorders in the central nervous system, which is triggered primarily by excessive Ca(2+) 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 neuro-toxicity 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.