Kainate, neurotoxic effect

Debonnel, G., Beauchesne, L., and de Montigny, C. 1989a. Domoic acid, the alleged mussel toxin, might produce its neurotoxic effect through kainate receptor activation an electrophysiological study in the dorsal hippocampus. CanJ Physiol Pharmacol 67, 29-33. 

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... 

The maturity of brain plays an important role in neuronal vulnerability to excitotoxins. The CVO regions and neural retina of immature rats and mice (less than 10 days of age) are much more sensitive to peripherally administered excitotoxins than the adult. In contrast, the striatum of the neonatal rat is remarkably resistant to doses of kainic acid that produce extensive lesions in the adult but full vulnerability is attained by three weeks after birth (Campochiaro and Coyle, 1978). Similarly, Honnegar and Richelson (1977) have found that reaggregating brain cultures exhibit increasing sensitivity to the neurotoxic effects of kainic acid with differentiation. At the other extreme, neuronal sensitivity of the striatum to directly injected kainate appears to increase with advancing age (Gaddy et aL, 1979). An age dependence for the neurotoxic action of ibotenic acid and other directly injected excitotoxins has not yet been described. 

Cannabidiol and THC reduced neurotoxicty induced by glutamate in cortical neurons (Hampson et al. 1998). This result was effective for toxicity induced at both NMDA and AMPA/kainate receptors, and was independent of cannabinoid receptor activity. The mechanism of neuroprotection appears to be by their potent antioxidant activity. They were even more protective against glutamate neurotoxicity than either ascorbate or o-tocopherol. 

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