Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy.
Recent microdialysis studies of excitatory and inhibitory amino acid release associated with paroxysmal hippocampal activity have found significant increases in the hippocampus of epileptic patients, but minimal or variable increases in animal models. One possible reason for the difference is that the animal models employed in these studies have not adequately reflected the pathophysiology of human epilepsy. The present study sought to verify the amino acid release reported in human epileptic hippocampus and then employs animal studies using a chronic rat model of epilepsy, in which rats exhibit spontaneous seizure activity 3 to 4 months after injection of kainic acid into the hippocampus. In agreement with earlier reports, we found increases in glutamate, aspartate and GABA during seizures in human hippocampus. In addition we found increases in taurine which have not previously been reported. The chronic rat model shows increases in the same amino acids as in the human epileptic hippocampus, both during spontaneous seizures and stimulation evoked after-discharges (ADs). In contrast, minimal increases are elicited by hippocampal stimulation in control (non-kainate injected) animals. These results correlate with the degree of mossy fiber reorganization found in the dentate gyrus of kainate rats or epileptic humans.
Wilson
C L
CL
Department of Neurology, UCLA School of Medicine 90024, USA.
Maidment
N T
NT
Shomer
M H
MH
Behnke
E J
EJ
Ackerson
L
L
Fried
I
I
Engel
J
J
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D018846:Excitatory Amino Acids / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D018846:Excitatory Amino Acids; D013654:Taurine; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid