Kainic acid neurotoxicity

Frandsen A., Krogsgaard-Larsen P., and Schousboe A. (1990). Novel glutamate receptor antagonists selectively protect against kainic acid neurotoxicity in cultured cerebral cortex neurons. J. Neurochem. 55 1821-1823. 

Biziere, K., and Coyle, J. T., 1978a, Influence of cortico-striatal afferents on striatal kainic acid neurotoxicity, Neurosci. Lett. 8 303-310. 

Nadler, J. V., and Cuthbertson, G. J., 1980, Kainic acid neurotoxicity toward hippocampal formation dependence on specific excitatory pathways. Brain Res. 195 47-56. 

ASP is caused by eating shellfish contaminated with one or more of three domoic acid derivatives, which are excitatory neurotoxic amino acids (Baden and Trainer, 1993). Domoic acid is produced by the diatom Nitzchia pungens and accumulates in mussels, specifically Mytilus edulis (Baden and Trainer, 1993). Domoic acid is similar in structure to the excitatory dicarboxylic amino acid, kainic acid, and has an antagonistic effect at the glutamate receptor. Both... 

Akaike et al. have examined the neuroprotective properties of serofendic acid, a substance isolated from serum. The compound was found to protect neuronal cells from both glutamate and NO. This was attributed to the scavenging of OH radicals (from the decomposition of ONOO-) rather than NO itself.320 Indeed, Ueda and colleagues have demonstrated the formation of both NO and OH in neuronal cells upon stimulation of the NMDA receptor.321 These workers also trapped lipid radicals in the brains of rats undergoing seizures induced by the stimulation of a subset of glutamate receptors with kainic acid. Polyphenols have been shown to exacerbate the neurotoxicity of NO.322... 

Coyle J. T. (1983). Neurotoxic action of kainic acid. J. Neurochem. 41 1-11. 

Non-NMDA-Glu-R (K-R) agonist (cf. Kainic acid) (iGlu-R, NMDA-Glu-R) [insecticidal, narcosis-potentiating, neurotoxic]... 

Neuropathological examination of the four patients who died indicated neuronal necrosis and astrocytosis, particularly in the hippocampus and the amygdaloid nucleus. All four victims also had lesions in the claustrum, secondary olfactory areas, the septal area, and the nucleus accumbens septi. Two had prominent thalamic damage, especially in the dorsal medial nucleus. The subfrontal cortex was also damaged in three of the patients. The authors noted that the pattern of damage in the hippocampus appeared to parallel that seen in animals that suffered neurotoxic reactions after administration of kainic acid (and domoic acid see above). 

Lee J Kim D Hong H Han S Kim J. Protective effect of etomidate on kainic acid-induced neurotoxicity in rat hippocampus. Neurosci. Lett. 2000, 286, 179-182. 

Decortication, which ablates the major excitatory and presumably glutamatergic pathway innervating the striatum (Divac et a/., 1977 Hattori et al.y 1979), protects against the neurotoxic action of kainic acid in the adult rat (Biziere and Coyle, 19786 McGeer et al.y 1978). Notably, the lesion is not immediately effective, but rather protection coincides with... 

Co-injection of glutamic acid with kainic acid, neither of which are neurotoxic in the decorticate striatum, partially restores kainate s neurotoxicity in this region (Biziere and Coyle, 1979). The essential role of these cortical afferents in the neurotoxic action of kainate has been conclusively established in tissue culture. Explants of striatum cultured alone are insensitive to the neurotoxic effects of kainic acid however, when the striatum is co-cultured with cortical explants resulting in the development of cortical innervation of the striatum, kainate added to the culture medium is effective in lesioning the striatal neurons (Pannula, 1980 Whetsell et al, 1979). 

While most studies have focused on the acute and subacute neurotoxic effects of kainic acid within the straitum, one must also consider the longterm consequences of the excitotoxin lesion. Neurochemical and histologic analysis of the striatum nine months after in situ kainate injection has revealed a profound atrophy of the region congruent with the loss of the... 

Nadler and Cuthbertson (1980) have examined the effects of prior transection of hippocampal pathways on the pattern of neural vulnerability to kainic acid. Lesion of the entorhinal- (Kohler et al, 1978) or septo-hippocampal pathways protects dentate granule cells and most of the CA1 pyramidal cells from the neurotoxic effects of kainate injected into the hippocampus three days after the lesion. When both pathways are interrupted, the CA2 pyramidal cells also survive. However, disruption of the mossy fiber or commisural innervation to the hippocampus does not attenuate kainate s neurotoxicity on the hippocampal pyramidal cells. Notably, septal lesions that ablate the cell bodies of origin of the cholinergic... 

Coyle et aL, 1981). For example, ibotenic acid in doses of 10-20 nmol causes an extensive lesion of the injected hippocampal formation without causing seizures, whereas 140 nmol of iV-methyl-D-aspartate precipitates severe seizures but causes small lesions restricted to the hippocampal formation. Nevertheless, the convulsant and neurotoxic properties of kainic acid, at least within the limbic system, suggest that kainate may prove to be a particularly useful agent for probing basic mechanisms involved in epilepsy. 

The extensive studies carried out in vivo and in vitro on kainic acid have laid the groundwork for understanding its neurotoxic effects. Although neurons vary in their sensitivity to kainic acid, the acute neurotoxic effects appear highly specific for neuronal perikarya, but usually spare axons of passage and of termination as well as nonneuronal elements within the lesioned area under most circumstances. Some neurons are remarkably resistant to its neurotoxic effects, such as the neurons in the... 

The mechanisms responsible for the neurotoxic action of kainic acid are complex. In several well characterized brain regions, neuronal vulnerability reflects a cooperative interaction between the stimulation of specific receptors for kainic acid and the functional integrity of excitatory afferents. In the limbic system, which is particularly prone to the epileptogenic properties of kainic acid, neuronal vulnerability to this toxin is considerably enhanced either directly or indirectly by the seizures. Under certain circumstances, kainic acid may have direct toxic effects on neurons independent of synaptic input. These have been clearly demonstrated with cerebellar explants in culture in which the concentration of kainic acid was relatively high (Seil et aL, 1979). 

In comparative studies of the neurotoxic effects of NMDA and kainic acid in the hippocampal formation, we have found that NMDA is approximately 100-fold less potent as a neurotoxin than kainic acid on a molar basis (Zaczek et aL, 1981). The lesion associated with local injection of NMDA is limited to the injection site in the hippocampal formation and appears to uniformly affect all neuronal perikarya within its circumference. However, doses of NMDA effective in causing significant lesions in the dentate gyrus precipitated a severe electroencephalographic and behavioral seizure disturbance punctuated by frequent tonic-clonic convulsions occasionally resulting in death. Thus, the superiority of NMDA over kainic acid and ibotenic acid for intracerebral injection remains to be established. 

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