title: Increases in GABA concentrations during cerebral ischaemia: a microdialysis study of extracellular amino acids.
abstract: OBJECTIVE
  Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably gamma-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage.
  
  
  METHODS
  Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping.
  
  
  RESULTS
  During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005).
  
  
  CONCLUSIONS
  The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.
authors.affiliation: Academic Department of Neurosurgery, University of Cambridge, Box 167, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. p.hutch@which.net
authors.forename: P J
authors.initials: PJ
authors.lastname: Hutchinson
authors.forename: M T
authors.initials: MT
authors.lastname: O'Connell
authors.forename: P G
authors.initials: PG
authors.lastname: Al-Rawi
authors.forename: C R
authors.initials: CR
authors.lastname: Kett-White
authors.forename: A K
authors.initials: AK
authors.lastname: Gupta
authors.forename: L B
authors.initials: LB
authors.lastname: Maskell
authors.forename: J D
authors.initials: JD
authors.lastname: Pickard
authors.forename: P J
authors.initials: PJ
authors.lastname: Kirkpatrick
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology; D002545:Brain Ischemia / Q000175:diagnosis / Q000503:physiopathology*; D002408:Catheters, Indwelling; D002851:Chromatography, High Pressure Liquid; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D016489:Head Injuries, Closed / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D007427:Intracranial Pressure / Q000502:physiology; D008297:Male; D017551:Microdialysis / Q000295:instrumentation*; D013345:Subarachnoid Hemorrhage / Q000175:diagnosis / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018846:Excitatory Amino Acids; D005680:gamma-Aminobutyric Acid