ISSN:
1432-1106
Keywords:
Hypoglycemia
;
Neuronal death
;
N-methyl-D-aspartate
;
AMPA
;
Rat
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00227969
