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Development of brain damage after neonatal hypoxia-ischemia: Excitatory amino acids and cysteine

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Abstract

The aim of this study was to investigate the possible role of excitatory amino acids (EAAs) and cysteine in the development of brain damage after hypoxia-ischemia (HI) in neonates. In a rat model of neonatal HI, changes in extracellular (ec) amino acids in cerebral cortex were measured with microdialysis and correlated with the extent of brain damage at the site of probe placement. Extracellular concentrations of glutamate, aspartate and cysteine increased during HI and remained elevated during reperfusion. During HI the pattern of EAA changes was the same in the infarcted, undamaged and border zone regions. During reperfusion, however, the ec concentrations of glutamate, aspartate and cysteine were higher in infarcted and border zone areas compared to undamaged tissue. HI also produced a slight increase of tissue concentration of cysteine and decrease of tissue concentration of glutamate in parietal cortex of the HI hemisphere. The effect of cysteine on brain damage induced by HI and glutamate was also investigated. A subtoxic dose of cysteine potentiated glutamate toxicity in the arcuate nucleus and enhanced brain infarction after HI in neonatal rats. The results show that in neonatal HI the extracellular levels of EAAs during HI are not directly related to brain injury but the EAA levels during reflow predict the extent of infarction. Cysteine increases HI-induced brain injury and potentiates glutamate toxicity in neonatal rats. Speculatively, elevated level of cysteine during reperfusion may participate in the excitotoxic cascade leading to brain injury.

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Abbreviations

AMPA:

2-amino-3-(3-hydroxy-5-methylisoxasol-4-yl)propanoate

EAAs:

excitatory amino acids

HI:

hypoxia-ischemia

KA:

kainic acid

MAP 2:

microtubule-associated protein 2

MK-801:

(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate

NBQX:

2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline

NMDA:

N-methyl-D-aspartate

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Authors and Affiliations

  1. Dept. of Anatomy and Cell Biology, University of Göteborg, Medicinaregatan 3-5, S-413 90, Göteborg, Sweden

    M. Puka-Sundvall, E. Gilland, E. Bona, A. Lehmann, M. Sandberg & H. Hagberg

  2. Dept. of Obstetrics and Gynecology, University of Göteborg, 413 90, Göteborg, Sweden

    E. Gilland & H. Hagberg

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  1. M. Puka-Sundvall
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  2. E. Gilland
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  3. E. Bona
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  4. A. Lehmann
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  5. M. Sandberg
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Puka-Sundvall, M., Gilland, E., Bona, E. et al. Development of brain damage after neonatal hypoxia-ischemia: Excitatory amino acids and cysteine. Metab Brain Dis 11, 109–123 (1996). https://doi.org/10.1007/BF02069499

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