Protection against ischemic hippocampal CA1 damage in the rat with a new non-NMDA antagonist, NBQX.

N H Diemer; M B Jørgensen; Flemming Fryd Johansen; M Sheardown; T Honoré

Protection against ischemic hippocampal CA1 damage in the rat with a new non-NMDA antagonist, NBQX.

N H Diemer, M B Jørgensen, Flemming Fryd Johansen, M Sheardown, T Honoré

Research output: Contribution to journal › Journal article › Research › peer-review

105 Citations (Scopus)

Abstract

Two glutamate antagonists were tested in a rat model of complete, transient cerebral ischemia. Six days after 10 min ischemia the mean loss of hippocampal CA1 pyramidal neurones was 73%. Administration of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antagonist NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) reduced the pyramidal neurone loss to 1%, 11% and 15%, when given before, immediately after or 1 h after ischemia, respectively. MK-801 (dizocilpine), a competitive NMDA antagonist gave no protection in this model. We suggest that the AMPA receptor transduction mechanisms are sensitized by ischemia and that the postischemic blockade of the main glutamatergic input to the CA1 cells with NBQX impairs the deleterious effect of "normal" postischemic excitatory transmission.

Original language	English
Journal	Acta Neurologica Scandinavica
Volume	86
Issue number	1
Pages (from-to)	45-9
Number of pages	4
ISSN	0001-6314
Publication status	Published - 1992
Externally published	Yes

Bibliographical note

Keywords: Animals; Brain Damage, Chronic; Brain Ischemia; Cell Count; Hippocampus; Male; Nerve Degeneration; Neurons; Quinoxalines; Rats; Rats, Inbred Strains; Receptors, AMPA; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter

Cite this

@article{168375505e0e11dd8d9f000ea68e967b,

title = "Protection against ischemic hippocampal CA1 damage in the rat with a new non-NMDA antagonist, NBQX.",

abstract = "Two glutamate antagonists were tested in a rat model of complete, transient cerebral ischemia. Six days after 10 min ischemia the mean loss of hippocampal CA1 pyramidal neurones was 73%. Administration of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antagonist NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) reduced the pyramidal neurone loss to 1%, 11% and 15%, when given before, immediately after or 1 h after ischemia, respectively. MK-801 (dizocilpine), a competitive NMDA antagonist gave no protection in this model. We suggest that the AMPA receptor transduction mechanisms are sensitized by ischemia and that the postischemic blockade of the main glutamatergic input to the CA1 cells with NBQX impairs the deleterious effect of {"}normal{"} postischemic excitatory transmission.",

author = "Diemer, {N H} and J{\o}rgensen, {M B} and Johansen, {Flemming Fryd} and M Sheardown and T Honor{\'e}",

note = "Keywords: Animals; Brain Damage, Chronic; Brain Ischemia; Cell Count; Hippocampus; Male; Nerve Degeneration; Neurons; Quinoxalines; Rats; Rats, Inbred Strains; Receptors, AMPA; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter",

year = "1992",

language = "English",

volume = "86",

pages = "45--9",

journal = "Acta Neurologica Scandinavica",

issn = "0001-6314",

publisher = "Wiley-Blackwell",

number = "1",

}

TY - JOUR

T1 - Protection against ischemic hippocampal CA1 damage in the rat with a new non-NMDA antagonist, NBQX.

AU - Diemer, N H

AU - Jørgensen, M B

AU - Johansen, Flemming Fryd

AU - Sheardown, M

AU - Honoré, T

N1 - Keywords: Animals; Brain Damage, Chronic; Brain Ischemia; Cell Count; Hippocampus; Male; Nerve Degeneration; Neurons; Quinoxalines; Rats; Rats, Inbred Strains; Receptors, AMPA; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter

PY - 1992

Y1 - 1992

N2 - Two glutamate antagonists were tested in a rat model of complete, transient cerebral ischemia. Six days after 10 min ischemia the mean loss of hippocampal CA1 pyramidal neurones was 73%. Administration of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antagonist NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) reduced the pyramidal neurone loss to 1%, 11% and 15%, when given before, immediately after or 1 h after ischemia, respectively. MK-801 (dizocilpine), a competitive NMDA antagonist gave no protection in this model. We suggest that the AMPA receptor transduction mechanisms are sensitized by ischemia and that the postischemic blockade of the main glutamatergic input to the CA1 cells with NBQX impairs the deleterious effect of "normal" postischemic excitatory transmission.

AB - Two glutamate antagonists were tested in a rat model of complete, transient cerebral ischemia. Six days after 10 min ischemia the mean loss of hippocampal CA1 pyramidal neurones was 73%. Administration of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antagonist NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) reduced the pyramidal neurone loss to 1%, 11% and 15%, when given before, immediately after or 1 h after ischemia, respectively. MK-801 (dizocilpine), a competitive NMDA antagonist gave no protection in this model. We suggest that the AMPA receptor transduction mechanisms are sensitized by ischemia and that the postischemic blockade of the main glutamatergic input to the CA1 cells with NBQX impairs the deleterious effect of "normal" postischemic excitatory transmission.

M3 - Journal article

C2 - 1325729

SN - 0001-6314

VL - 86

SP - 45

EP - 49

JO - Acta Neurologica Scandinavica

JF - Acta Neurologica Scandinavica

IS - 1

ER -