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Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia

Nellgård, Bengt LU and Wieloch, Tadeusz LU (1992) In Experimental Brain Research 92(2). p.259-266
Abstract

Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg · kg-1 i.p., followed by an i.v. infusion of 225 μg · kg-1 · min-1 for 6 h; (2) the... (More)

Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg · kg-1 i.p., followed by an i.v. infusion of 225 μg · kg-1 · min-1 for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg · kg-1 given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg · kg-1 i.p., followed by an i.v. infusion of 225 μg · kg-1 · min-1 for 6 h), with dizocilpine 0.33 mg · kg-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40116 [D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] 10 mg · kg-1 given i.p.. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist. We conclude that neuronal damage continues to develop in the striatum and in cortical brain regions in the posthypoglycemic period and that both NMDA- and AMPA-receptors contribute to this process, possibly by a change in the cellular response to both AMPA- and NMDA-receptor stimulation.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AMPA, Hypoglycemia, N-methyl-D-aspartate, Neuronal death, Rat
in
Experimental Brain Research
volume
92
issue
2
pages
8 pages
publisher
Springer
external identifiers
  • scopus:0027070955
  • pmid:1362958
ISSN
0014-4819
DOI
10.1007/BF00227969
language
English
LU publication?
yes
id
1446f6af-11ae-40f9-b89f-1e3c73a851db
date added to LUP
2019-06-13 16:21:46
date last changed
2020-06-07 06:04:29
@article{1446f6af-11ae-40f9-b89f-1e3c73a851db,
  abstract     = {<p>Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg · kg<sup>-1</sup> i.p., followed by an i.v. infusion of 225 μg · kg<sup>-1</sup> · min<sup>-1</sup> for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg · kg<sup>-1</sup> given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg · kg<sup>-1</sup> i.p., followed by an i.v. infusion of 225 μg · kg<sup>-1</sup> · min<sup>-1</sup> for 6 h), with dizocilpine 0.33 mg · kg<sup>-1</sup> given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40116 [D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] 10 mg · kg<sup>-1</sup> given i.p.. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist. We conclude that neuronal damage continues to develop in the striatum and in cortical brain regions in the posthypoglycemic period and that both NMDA- and AMPA-receptors contribute to this process, possibly by a change in the cellular response to both AMPA- and NMDA-receptor stimulation.</p>},
  author       = {Nellgård, Bengt and Wieloch, Tadeusz},
  issn         = {0014-4819},
  language     = {eng},
  month        = {12},
  number       = {2},
  pages        = {259--266},
  publisher    = {Springer},
  series       = {Experimental Brain Research},
  title        = {Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia},
  url          = {http://dx.doi.org/10.1007/BF00227969},
  doi          = {10.1007/BF00227969},
  volume       = {92},
  year         = {1992},
}