Excitotoxic injury of the neostriatum: a model for Huntington's disease.
Intrastriatal lesions with excitatory amino acids mimic some of the neurochemical and neuropathological characteristics of Huntington's disease (HD); this has led to the hypothesis that an endogenous excitotoxin may be involved in the disease. Recent advances in understanding the metabolic pathways of endogenous excitotoxins and the distribution and function of excitatory amino acid receptors have helped to refine the excitotoxin hypothesis, which is still inadequate to explain some aspects of the disease. However, as an experimental model for producing neuronal depletion in the neostriatum, excitotoxic injury has allowed the study of other neuronal characteristics of HD such as progressive atrophy and regeneration; it has also permitted extensive exploration of the anatomical and functional recovery induced by intrastriatal grafts. Moreover, adaptation of the rodent model to the non-human primate has enabled investigators to examine lesion-induced motor dysfunctions that are more comparable to those in HD. Thus, beyond its potential importance in the pathogenesis of HD, excitotoxic injury as an experimental tool promises to help further elucidate the pathological and functional alterations characteristic of the disease.
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Department of Neurology, Massachusetts General Hospital, Boston.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter