title: Chronic intrastriatal injection of the excitatory amino acid receptor antagonist L-kynurenic acid in rat produces selective neuron sparing lesions.
abstract: Heritable neurodegenerative diseases may be associated with one or more endogenous neurotoxins whose actions on neurons lead to the degenerative changes. One metabolite of tryptophan, the amino acid L-kynurenic acid (L-KYN), was chronically injected into the striatum of the male rat to test its potential as an endogenous neurotoxin. L-KYN, at concentrations of approximately five times its normal brain levels, produced a large lesion with relative selective neuron sparing. The L-KYN-induced lesion presented three concentric regions: a central necrotic zone, a thin pyknotic zone, and an outermost spongiose zone. The number of GABA-ergic neurons were markedly reduced (approximately 76%), while cholinesterase-positive neurons were also lost. The NADPH diaphorase-positive neurons were the most resistant to L-KYN neurotoxicity and were spread throughout the spongiose zone. The brain levels of L-KYN are abnormal in patients with the neurodegenerative disorder Huntington's disease and as a neurotoxin L-KYN may play a role in the etiology of this disease. Of further significance, the fact that L-KYN is neurotoxic contraindicates the use of this excitatory amino acid receptor antagonist as a therapeutic agent in the treatment of neurodegenerative disorders.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, University of North Dakota, Grand Forks 58201.
authors.forename: G K
authors.initials: GK
authors.lastname: Rieke
mesh_terms: D000818:Animals; D002802:Cholinesterases / Q000032:analysis; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009252:NADPH Dehydrogenase / Q000032:analysis; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013238:Stereotaxic Techniques; D005680:gamma-Aminobutyric Acid / Q000032:analysis
chemical_list: D005680:gamma-Aminobutyric Acid; D009252:NADPH Dehydrogenase; D002802:Cholinesterases; D007736:Kynurenic Acid