In vivo brain dialysis of amino acids and simultaneous EEG measurements following intrahippocampal quinolinic acid injection: evidence for a dissociation between neurochemical changes and seizures.
The extracellular content of taurine, glutamate, glutamine, and glycine was measured by the novel method of brain dialysis in the acute phases following an intrahippocampal injection of the excitotoxic convulsant brain metabolite quinolinic acid (QUIN). Using bilaterally implanted depth electrodes physically combined with hollow fibers for dialysis, it was possible to collect continuously brain perfusates while simultaneously monitoring brain activity in the unanesthetized rat. In separate animals, hippocampal amino acid tissue levels were measured 2 h after an intracerebral injection of a convulsant dose (156 nmol) of QUIN. When compared with those in animals receiving the nonconvulsant decarboxylation product of QUIN, nicotinic acid, no differences in tissue levels were detected. In contrast, the same dose of QUIN caused a selective increase (2.24-fold) in taurine levels in perfusates from the injected hippocampus. These changes were apparent prior to the onset of electrographic seizures and did not occur in the contralateral hippocampus where seizure activity was equally severe. Thus, increases in extracellular taurine, triggered by the presence of QUIN in the hippocampus, may reflect a selective tissue response to the neurotoxic (rather than the convulsant) effects of this excitotoxin.
Vezzani
A
A
Ungerstedt
U
U
French
E D
ED
Schwarcz
R
R
D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D001224:Aspartic Acid / Q000032:analysis; D001921:Brain / Q000503:physiopathology; D003956:Dialysis; D004569:Electroencephalography; D005973:Glutamine / Q000032:analysis; D005998:Glycine / Q000032:analysis; D006624:Hippocampus / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D009525:Niacin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D013654:Taurine / Q000032:analysis; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D000596:Amino Acids; D011725:Pyridines; D011805:Quinolinic Acids; D005973:Glutamine; D013654:Taurine; D009525:Niacin; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D017378:Quinolinic Acid; D005998:Glycine