Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia
(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.
(Less)
- author
- Nellgård, Bengt LU and Wieloch, Tadeusz LU
- organization
- publishing date
- 1992-12-01
- 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
-
- pmid:1362958
- scopus:0027070955
- 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
- 2024-01-01 10:18:03
@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}},
keywords = {{AMPA; Hypoglycemia; N-methyl-D-aspartate; Neuronal death; Rat}},
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}},
}