ABSTRACT. An imbalance of excitatory and inhibitory transmitters in the brain has been suggested to cause epileptic seizures. In this study, we investigated the kinetics of glutamate (GLU) and γ-aminobutyric acid (GABA) in cerebrospinal fluid (CSF-GLU and CSF-GABA, respectively) using a high performance liquid chromatography (HPLC) in a canine model of complex partial status epilepticus (CPSE) induced by the microinjection of kainic acid (KA) into the unilateral amygdala. During the acute phase (3, 6, 12 and 48 hr after the onset of CPSE), CSF-GLU was significantly increased, while CSF-GABA was decreased, although not significantly. In the chronic phase, both CSF-GLU and CSF-GABA were significantly lower than normal at 72 hr after the onset of CPSE, and their levels returned to normal at 2 months. Results of the present study demonstrate that CSF-GLU is gradually increased in relation with seizure severity, and suggested the possibility that CSF-GABA was consistently decreased during CPSE induced by KA in dogs. KEY WORDS: cerebrospinal fluid, GABA, glutamate, kainic acid, status epilepticus.J. Vet. Med. Sci. 66(12): 1555-1559, 2004 It is well accepted that glutamate (GLU) and aspartate (ASP) are the main excitatory amino acids in the brain, while γ-aminobutyric acid (GABA) functions as an inhibitory neurotransmitter [9,15]. An imbalance between excitatory and inhibitory amino acids has been hypothesized as a possible mechanism for epileptic seizures, thus amino acid analysis in the cerebrospinal fluids (CSFs) has been employed for understanding the pathogenesis of epilepsy. Numerous articles reported concentrations of GLU and GABA in the CSF and/or brain tissues in human epileptic patients and/or experimental animal models, which were quite inconsistent [2-4, 7-9, 12, 15, 18]. On the other hand, in veterinary medicine, only a few reports deal with amino acid concentrations in the CSF [1,11,16,17]. Podell and Hadjiconstantinou [16,17] reported the concentrations of GLU and GABA in the CSF from dogs with idiopathic epilepsy, suggesting a diagnostic potential for the amino acid analysis.Previously, we reported the clinical, electrophysiological and pathological characteristics of a canine model of complex partial status epilepticus (CPSE) induced by a microinjection of kainic acid (KA) into the unilateral amygdala [5]. We also conducted further studies of this model using magnetic resonance imaging (MRI) [6]. These reports clearly demonstrated that our canine KA-induced CPSE model is valuable for investigating the status epilepticus-induced brain damage (excitotoxicity theory), as well as for characterizing the specificity of epilepsy in the dog. In this study, to examine the relationship between CPSE and neurotransmitters, we characterized the kinetics of GLU and GABA in the CSF (CSF-GLU and CSF-GABA, respectively) in the KA-induced CPSE-model dogs.
MATERIALS AND METHODSThis study was performed in conformity with the Animal Care and Use Committee of Nippon Veterinary and Animal Science University.Normal animals: ...