Glutamate neurotoxicity

Dawson, V.L., Dawson, T.M., London, E.D., Bredt, D.S. and Snyder, S.H. (1991). Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc. Natl Acad. Sci. USA 88, 6368-6371. 

Choi, D. W. and Rothman, S. M. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Anna. Rev. Neurosci. 13 171-182,1990. 

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. 

Zhu L, Wu J, Liao FI, Gao J, Zhao XN, Zhang ZX. (1997). Antagonistic effects of extract from leaves of Ginkgo biloba on glutamate neurotoxicity. Chung Kuo Yao Li Hsueh Pao. 18(4) 344-47. 

Several toxins may also alter the mechanisms that need the excitatory action of glutamate. Neurotoxicity mechanisms by excitatory amino acids can be of two types ... 

Increase of free cytosolic calcium is toxic for various reasons. Among them are the diminution of ATP levels (Tsuji et al. 1994), the protease and lipase activation, and the FR production that causes a peroxidation of lipids. The inflow of calcium in the terminals could also increase the release of endogenous excitatory amino acids and propagate neuronal damage through positive feedback (Choi and Hartley 1993). Glutamic neurotoxicity mediated by calcium follows three stages ... 

Eye function It protects retinal neurons against N-methyl-D-aspartate receptor mediated glutamate neurotoxicity. Deterioration of accommodation following visual work has also been shown to improve in individuals receiving methylcobalamin. 

Attention then turned to the mechanism of glutamate-induced neurotoxicity in the brain. Evidence was provided that NO mediates glutamate neurotoxicity in primary cortical cultures (Dawson et ai, 1991). NO synthase inhibitors and hemoglobin prevented NMDA- and glutamate-induced neurotoxicity on the other hand, L-arginine reversed the effect of NO synthase inhibitors, and sodium nitroprusside (which decomposes to NO) caused neurotoxicity that paralleled cyclic GMP formation. In the cerebral cortex, NO synthase immunoreactivity was found to be confined to a discrete population of aspiny neurons comprising... 

Choi D. W. (1988). Glutamate neurotoxicity and diseases of the nervous system. Neuron 1 628-634. 

Llansola M., Monfort P., and Felipo V. (2000). Inhibitors of phospholipase C prevent glutamate neurotoxicity in primary cultures of cerebellar neurons. J. Pharmacol. Exp. Ther. 292 870-876. 

Almeida A., Heales S. J., Bolanos J. P., and Medina J. M. (1998). Glutamate neurotoxicity is associated with nitric oxide-mediated mitochondrial dysfunction and glutathione depletion. Brain Res. 790 209-216. 

Atlante A., Gagliardi S., Minervini G. M., Ciotti M. T., Marra E., and Calissano P. (1997). Glutamate neurotoxicity in rat cerebellar granule cells A major role for xanthine oxidase in oxygen radical formation. J. Neurochem. 68 2038-2045. 

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