Kynurenate inhibition of cell excitation decreases stroke size and deficits

Isabelle M. Germano; Lawrence H. Pitts; Brian S. Meldrum; Henry M. Bartkowski; Roger P. Simon

doi:10.1002/ana.410220609

Kynurenate inhibition of cell excitation decreases stroke size and deficits

Isabelle M. Germano, Lawrence H. Pitts, Brian S. Meldrum, Henry M. Bartkowski, Roger P. Simon

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163 Scopus citations

Abstract

Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global ischemia/reperfusion and hypoglycemia. The current investigations extend these observations to a model of focal ischemia. Kynurenic acid, a broad‐spectrum antagonist at excitatory amino acid receptors, was used as treatment (300 mg/kg; 3 doses at 4‐hour intervals) before and after focal cerebral ischemia in rats (n = 54). Preischemia but not 1 hour postischemia treatment with kynurenate attenuated infarction size (p < 0.001) and improved neurological outcome (p < 0.001) studied at 24 hours after injury. These data support the role of excitatory neurotransmission in acute neuronal injury and support pharmacological inhibition of cell excitation as a potential therapy for stroke.

Original language	English
Pages (from-to)	730-734
Number of pages	5
Journal	Annals of Neurology
Volume	22
Issue number	6
DOIs	https://doi.org/10.1002/ana.410220609
State	Published - Dec 1987
Externally published	Yes

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title = "Kynurenate inhibition of cell excitation decreases stroke size and deficits",

abstract = "Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global ischemia/reperfusion and hypoglycemia. The current investigations extend these observations to a model of focal ischemia. Kynurenic acid, a broad‐spectrum antagonist at excitatory amino acid receptors, was used as treatment (300 mg/kg; 3 doses at 4‐hour intervals) before and after focal cerebral ischemia in rats (n = 54). Preischemia but not 1 hour postischemia treatment with kynurenate attenuated infarction size (p < 0.001) and improved neurological outcome (p < 0.001) studied at 24 hours after injury. These data support the role of excitatory neurotransmission in acute neuronal injury and support pharmacological inhibition of cell excitation as a potential therapy for stroke.",

author = "Germano, {Isabelle M.} and Pitts, {Lawrence H.} and Meldrum, {Brian S.} and Bartkowski, {Henry M.} and Simon, {Roger P.}",

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AU - Germano, Isabelle M.

AU - Pitts, Lawrence H.

AU - Meldrum, Brian S.

AU - Bartkowski, Henry M.

AU - Simon, Roger P.

PY - 1987/12

Y1 - 1987/12

N2 - Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global ischemia/reperfusion and hypoglycemia. The current investigations extend these observations to a model of focal ischemia. Kynurenic acid, a broad‐spectrum antagonist at excitatory amino acid receptors, was used as treatment (300 mg/kg; 3 doses at 4‐hour intervals) before and after focal cerebral ischemia in rats (n = 54). Preischemia but not 1 hour postischemia treatment with kynurenate attenuated infarction size (p < 0.001) and improved neurological outcome (p < 0.001) studied at 24 hours after injury. These data support the role of excitatory neurotransmission in acute neuronal injury and support pharmacological inhibition of cell excitation as a potential therapy for stroke.

AB - Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global ischemia/reperfusion and hypoglycemia. The current investigations extend these observations to a model of focal ischemia. Kynurenic acid, a broad‐spectrum antagonist at excitatory amino acid receptors, was used as treatment (300 mg/kg; 3 doses at 4‐hour intervals) before and after focal cerebral ischemia in rats (n = 54). Preischemia but not 1 hour postischemia treatment with kynurenate attenuated infarction size (p < 0.001) and improved neurological outcome (p < 0.001) studied at 24 hours after injury. These data support the role of excitatory neurotransmission in acute neuronal injury and support pharmacological inhibition of cell excitation as a potential therapy for stroke.

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Kynurenate inhibition of cell excitation decreases stroke size and deficits

Abstract

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