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Spinal neuronal pathology associated with continuous intrathecal infusion of N-methyl-D-aspartate in the rat.

Abstract：

:Continuous intrathecal infusion of N-methyl-D-aspartate (NMDA) at the level of the lumbar enlargement of the spinal cord in middle-aged rats produced dose-dependent toxicity of spinal cord neuronal systems. Toxicity was enhanced by coadministration of glycine, but was significantly reduced when NMDA was co-administered with the competitive inhibitor DL-2-amino-5-phosphovaleric acid or the noncompetitive inhibitor MgSO4. The toxic effects of NMDA were manifest most dramatically and at the lowest concentrations in the neuropil, while neuronal loss was obvious at higher concentrations. The distribution and intensity of reactive astrocytosis was consistent with the known regional and subcellular distribution of NMDA receptors in the spinal cord of rats. The increase in ribosomes and rough endoplasmic reticulum observed in anterior horn cells suggested an increase of cell metabolism reflecting either a nonspecific response to injury or a specific increase in cell metabolism secondary to sustained activation of NMDA receptors. The present studies implicate excitatory amino acid receptors of the NMDA type in producing toxicity to selected neuronal populations of the spinal cord. This model provides a system for studies of the protective effects and rescue of neuronal populations susceptible to the toxic effects of excitatory amino acids.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Nag S,Riopelle RJ

doi

10.1007/BF00662631

subject

Has Abstract

pub_date

1990-01-01 00:00:00

pages

7-13

issue

1

eissn

0001-6322

issn

1432-0533

journal_volume

81

pub_type

杂志文章

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