title: Effect of treatment with simvastatin and cyclosporine on neurotransmitter concentrations in cerebrospinal fluid after subarachnoid hemorrhage in dogs.
abstract: OBJECTIVE
  To measure concentrations of glutamate, aspartate, γ-aminobutyric acid (GABA), and glycine in CSF of dogs with experimentally induced subarachnoid hemorrhage (SAH) and to assess effects of cyclosporine and simvastatin on these concentrations.
  
  
  METHODS
  CSF samples from 13 dogs.
  
  
  METHODS
  In a previous study, SAH was induced in dogs via 2 injections of autologous blood into the cerebellomedullary cistern 24 hours apart. Dogs were untreated (control; n = 5) or received simvastatin alone (4) or simvastatin in combination with cyclosporine (4). Samples of CSF were collected before the first blood injection (baseline; time 0), before the second blood injection, and on days 3, 7, and 10. For the study reported here, neurotransmitter concentrations in CSF were analyzed via high-performance liquid chromatography. Data were analyzed with a repeated-measures model with adjustments for multiple comparisons by use of the Tukey method.
  
  
  RESULTS
  In control dogs, the glutamate concentration peaked on day 3 and there was a significant increase in GABA and glutamate concentrations. Glutamate concentrations were significantly lower and glycine concentrations significantly higher on day 3 after administration of simvastatin alone or simvastatin in combination with cyclosporine, compared with concentrations for the control group. No significant differences in GABA and aspartate concentrations were detected among treatment groups at any time point.
  
  
  CONCLUSIONS
  Glutamate concentrations were increased in the CSF of dogs with SAH. Simvastatin administration attenuated high glutamate concentrations. A combination of immunosuppression and upregulation of nitric oxide synthase may be useful in lowering high glutamate concentrations in ischemic CNS conditions.
authors.affiliation: Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. srplatt@uga.edu
authors.forename: Simon R
authors.initials: SR
authors.lastname: Platt
authors.forename: Joan R
authors.initials: JR
authors.lastname: Coates
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Eifler
authors.forename: Gaylen L
authors.initials: GL
authors.lastname: Edwards
authors.forename: Marc
authors.initials: M
authors.lastname: Kent
authors.forename: Ketan R
authors.initials: KR
authors.lastname: Bulsara
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid*; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000662:veterinary*; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016572:Cyclosporine; D019821:Simvastatin