title: Striatal outflow of adenosine, excitatory amino acids, gamma-aminobutyric acid, and taurine in awake freely moving rats after middle cerebral artery occlusion: correlations with neurological deficit and histopathological damage.
abstract: OBJECTIVE
  While a number of studies have investigated transmitter outflow in anesthetized animals after middle cerebral artery occlusion (MCAO) performed by craniectomy, studies have never been performed after MCAO induced by intraluminal filament. In addition, it has been reported that after MCAO, infarct volume correlates with functional outcome and with transmitter outflow, although there are no studies that demonstrate a direct correlation between transmitter outflow and functional outcome. The purpose of the present study was to assess excitatory amino acids, gamma-aminobutyric acid, taurine, and adenosine outflow in awake rats after intraluminal MCAO and to determine whether, in the same animal, outflow was correlated with neurological outcome and histological damage.
  
  
  METHODS
  Vertical microdialysis probes were placed in the striatum of male Wistar rats. After 24 hours, permanent MCAO was induced by the intraluminal suture technique. The transmitter concentrations in the dialysate were determined by high-performance liquid chromatography. Twenty-four hours after MCAO, neurological deficit and histological outcome were evaluated.
  
  
  RESULTS
  All transmitters significantly increased after MCAO. Twenty-four hours after MCAO, the rats showed a severe sensorimotor deficit and massive ischemic damage in the striatum and in the cortex (9+/-2% and 25+/-6% of hemispheric volume, respectively). Significant correlations were found between the efflux of all transmitters, neurological score, and striatal infarct volume.
  
  
  CONCLUSIONS
  In this study, for the first time, amino acid and adenosine extracellular concentrations during MCAO by the intraluminal suture technique were determined in awake and freely moving rats, and a significant correlation was found between transmitter outflow and neurological deficit. The evaluation of neurological deficit, histological damage, and transmitter outflow in the same animal may represent a useful approach for studying neuroprotective properties of new drugs/agents against focal ischemia.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Melani
authors.forename: L
authors.initials: L
authors.lastname: Pantoni
authors.forename: C
authors.initials: C
authors.lastname: Corsi
authors.forename: L
authors.initials: L
authors.lastname: Bianchi
authors.forename: A
authors.initials: A
authors.lastname: Monopoli
authors.forename: R
authors.initials: R
authors.lastname: Bertorelli
authors.forename: G
authors.initials: G
authors.lastname: Pepeu
authors.forename: F
authors.initials: F
authors.lastname: Pedata
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D018846:Excitatory Amino Acids / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017551:Microdialysis / Q000295:instrumentation; D020768:Middle Cerebral Artery / Q000378:metabolism*; D009460:Neurologic Examination; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013536:Suture Techniques; D013654:Taurine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018846:Excitatory Amino Acids; D018377:Neurotransmitter Agents; D013654:Taurine; D005680:gamma-Aminobutyric Acid; D000241:Adenosine