+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Protective effects of the glutamate antagonist MK-801 on pyrithiamine-induced lesions and amino acid changes in rat brain



Protective effects of the glutamate antagonist MK-801 on pyrithiamine-induced lesions and amino acid changes in rat brain



Journal of Neuroscience 10(5): 1664-1674



An acute bout of pyrithiamine-induced thiamine deficiency (PTD) produces pathologic lesions within thalamus, mammillary body, and periventricular regions of rat brain. The biological bases for these pathologic changes and their selective distribution within the brain are unclear. The type of tissue damage observed within the thalamus of PTD rats closely resembles that observed following anoxic-ischemic insults and suggests the involvement of excitotoxic amino acids in its pathogenesis. The effects of the N-methyl-D-aspartate receptor antagonist MK-801 (3 mg/kg, i. p.) on brain lesions and amino acid changes have been assessed in rats killed during the late acute stages of PTD. A marked loss of neurons within midline intralaminar nuclei and the posterior nuclear group of the thalamus were observed in the early acute stage of PTD treatment. In the late acute stage, these changes were present throughout the entire thalamus and extended caudally to the periacqueductal gray and mesencephalic tegmentum. Hemorrhagic lesions were observed only in the late acute group and were the primary lesion within the mammillary body and medial and lateral geniculates. No pathologic changes were observed in hippocampus, amygdala, and cortex. MK-801 administered during the late stages resulted in a marked attenuation of necrotic damage to thalamus and periacqueductal gray and a reduction in the number and size of hemorrhagic lesions. Significant reductions of aspartate and glutamate and increases of glycine were observed in 5 regions of thalamus, the hippocampus, hypothalamus, and mammillary bodies of both the early and late acute PTD groups. Levels of GABA and taurine in caudal areas were significantly elevated in the early acute stage but were unchanged from controls in the late acute group. These amino acid changes were reduced in the MK-801 treated late acute group. These observations suggest that NMDA receptors are involved the pathogenesis of PTD-induced brain lesions and that nuclei of the intralaminar and posterior nuclear groups are most vulnerable to PTD effects.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 041108928

Download citation: RISBibTeXText

PMID: 1970604


Related references

Protective effects of the glutamate antagonist Mk-801 on pyrithiamine- induced lesions and amino acid changes in rat brain. The Journal of Neuroscience 10(5): 1664-1674, 1990

Proto-oncogene c-fos induction in thiamine-deficient encephalopathy. Protective effects of nicardipine on pyrithiamine-induced lesions. Journal of the Neurological Sciences 118(2): 175-180, 1993

Gamma amino butyric acid trans aminase and glutamic acid decarboxylase changes in brain of rats treated with pyrithiamine. Journal of Neurochemistry 41(Suppl.): S28, 1983

Glutamate-evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue. British Journal of Pharmacology 90(4): 641-650, 1987

The antagonist effect of alpha-amino-pimelic acid on glutamate-induced inhibitions of Helix neurones. Brain Research 86(1): 139-143, 1975

The effects of a thlamlne antagonist, pyrithiamine, on levels of selected metabolic intermediates and on activities of thiamine-dependent enzymes in brain and liver. Jneurochem 15(7): 621-631, 1968

MK-801 prevents brain lesions and delayed-nonmatching-to-sample deficits produced by pyrithiamine-induced encephalopathy in rats. Behavioral Neuroscience 106(4): 623-633, 1992

Antagonist properties of a phosphono isoxazole amino acid at glutamate R1-4 -2-amino-3- propionic acid receptor subtypes. Molecular Pharmacology 53(3): 590-596, 1998

Antagonist Properties of a Phosphono Isoxazole Amino Acid at Glutamate R14 ( R,S )-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid Receptor Subtypes. Molecular Pharmacology 53(3): 590-596, 1998

Synthesis and protective effect of 1 3 5 triazine derivatives leukotriene c 4 antagonist on hydrochloric acid ethanol induced gastric lesions in rats. Chemical & Pharmaceutical Bulletin 39(12): 3181-3182, 1991

Serotonin-1A receptor stimulation mediates effects of a metabotropic glutamate 2/3 receptor antagonist, 2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9-yl)propanoic acid (LY341495), and an N-methyl-D-aspartate receptor antagonist, ketamine, in the novelty-suppressed feeding test. Psychopharmacology 231(11): 2291-2298, 2014

Protective effects of resveratrol on glutamate-induced damages in murine brain cultures. Journal of Neural Transmission 120(9): 1271-1280, 2013

Effects of intra ventricular gamma acetylenic gamma amino butyric acid on gamma amino butyric acid concentrations gamma amino butyric acid trans aminase and glutamate decarboxylase in several areas of the chick brain. Majkowski, J. Monographs In Neural Sciences, Vol. 5. Epilepsy: A Clinical And Experimental Research; Proceedings Of The 2nd European Regional Conference On Epilepsy, Warsaw, Poland, Oct. 5-7, . Xvi 306p. S. Karger: Basel, Switzerland; New York, N.y., Usa. Illus. Paper. P34-39, 1980, 1981

Phencyclidine-like behavioral effects in pigeons induced by systemic administration of the excitatory amino acid antagonist, 2-amino-5-phosphonovalerate. Life Sciences 39(11): 973-978, 1986

Effects of the glutamate receptor antagonist, MK-801, on kainic acid induced cytokine expression. Society for Neuroscience Abstracts 25(1-2): 1445, 1999