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Inhibitory and excitatory neurotransmitters in the cerebrospinal fluid of epileptic dogs

Claudia EllenbergerDivision of Clinical Neurology, Department of Clinical Veterinary Medicine, Faculty of Veterinary Medicine, University of Bern, Switzerland.

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Meike MevissenInstitute of Veterinary Pharmacology, Faculty of Veterinary Medicine, University of Bern, Switzerland.

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Marcus DoherrDivision of Clinical Research, Department of Clinical Veterinary Medicine, Faculty of Veterinary Medicine, University of Bern, Switzerland.

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Günter ScholtysikInstitute of Veterinary Pharmacology, Faculty of Veterinary Medicine, University of Bern, Switzerland.

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André JaggyDivision of Clinical Neurology, Department of Clinical Veterinary Medicine, Faculty of Veterinary Medicine, University of Bern, Switzerland.

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Abstract

Objective—To determine concentrations of excitatory and inhibitory amino acids in CSF of a large number of dogs with idiopathic epilepsy or genetic epilepsy and to evaluate changes in CSF amino acid concentration with regard to drug treatment and sex.

Animals—35 Labrador Retrievers with genetic epilepsy (20 male and 15 female), 94 non-Labrador Retrievers with idiopathic epilepsy (71 male and 23 female), and 20 control dogs (10 male and 10 female).

Procedure—Collection of CSF was performed > 72 hours after the occurrence of seizures. Cerebrospinal fluid concentrations of γ-aminobutyric acid (GABA), glutamate (GLU), aspartate (ASP), serine, and glycine were determined by use of high performance liquid chromatography with electrochemical detection.

Results—CSF concentrations of GABA and GLU were significantly lower in Labrador Retrievers with genetic epilepsy (LR-group dogs) than in control-group dogs or in non-Labrador Retrievers with idiopathic epilepsy (non–LR-group dogs). The GLU-to-GABA ratio was significantly higher in LR-group dogs than in non–LR-group dogs. CSF concentrations of GLU and ASP were significantly lower when all dogs with epilepsy (non–LR- and LR-group dogs combined) were compared with control-group dogs.

Conclusions and Clinical Relevance—A decrease in CSF concentrations of GABA appears to play a role in the pathogenesis of genetically determined epilepsy in Labrador Retrievers. However, this decrease in CSF concentrations of GABA may also be a consequence of seizure activity. The GLU-to-GABA ratio may prove to be a useful indicator of genetic epilepsy in Labrador Retrievers. (Am J Vet Res 2004;65:1108–1113)

Abstract

Objective—To determine concentrations of excitatory and inhibitory amino acids in CSF of a large number of dogs with idiopathic epilepsy or genetic epilepsy and to evaluate changes in CSF amino acid concentration with regard to drug treatment and sex.

Animals—35 Labrador Retrievers with genetic epilepsy (20 male and 15 female), 94 non-Labrador Retrievers with idiopathic epilepsy (71 male and 23 female), and 20 control dogs (10 male and 10 female).

Procedure—Collection of CSF was performed > 72 hours after the occurrence of seizures. Cerebrospinal fluid concentrations of γ-aminobutyric acid (GABA), glutamate (GLU), aspartate (ASP), serine, and glycine were determined by use of high performance liquid chromatography with electrochemical detection.

Results—CSF concentrations of GABA and GLU were significantly lower in Labrador Retrievers with genetic epilepsy (LR-group dogs) than in control-group dogs or in non-Labrador Retrievers with idiopathic epilepsy (non–LR-group dogs). The GLU-to-GABA ratio was significantly higher in LR-group dogs than in non–LR-group dogs. CSF concentrations of GLU and ASP were significantly lower when all dogs with epilepsy (non–LR- and LR-group dogs combined) were compared with control-group dogs.

Conclusions and Clinical Relevance—A decrease in CSF concentrations of GABA appears to play a role in the pathogenesis of genetically determined epilepsy in Labrador Retrievers. However, this decrease in CSF concentrations of GABA may also be a consequence of seizure activity. The GLU-to-GABA ratio may prove to be a useful indicator of genetic epilepsy in Labrador Retrievers. (Am J Vet Res 2004;65:1108–1113)