title: Glutamine synthetase protects the spinal cord against hypoxia-induced and GABA(A) receptor-activated axonal depressions.
abstract: BACKGROUND
  We investigated the effects of exogenous GS on hypoxia- and GABA(A) receptor-induced axonal depression in neonatal rats.
  
  
  METHODS
  To assess the effects of GS on spinal cord axons, CAPs were recorded. Hemicords were exposed to hypoxia by 30-minute superfusion with Ringer's solution saturated with 95% N(2) and 5% CO(2) followed by 60-minute exposure to 95% N(2) and 5% CO(2) gassing (N(2) gassing phase) and then 90 minutes of resuperfusion with oxygenated Ringer's solution (resuperfusion phase). Exogenous high GS (15 U) or low GS (1.5 U) was delivered during the N(2) gassing phase. The effects of GS on GABA(A) receptor-induced axonal depression were analyzed with oxygenated isolated dorsal columns.
  
  
  RESULTS
  The high GS significantly reduced the decline in the CAP amplitudes during the N(2) gassing and resuperfusion phases (P = .0185) compared to the hypoxia control. The low GS treatment showed a trend toward recovery during the N(2) gassing and resuperfusion phases, but the effect was not significant (P = .3953). In isolated dorsal columns, GS significantly reduced the CAP amplitude depression induced by GABA(A) receptor agonist.
  
  
  CONCLUSIONS
  Our findings suggest that GS had dose-dependent protective effects on the spinal cord against hypoxia-induced axonal depression. It may inhibit the depression of CAP amplitudes by blocking GABA(A) receptors.
authors.affiliation: WM Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA. mat@fmu.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Wise
authors.initials: W
authors.lastname: Young
authors.forename: Namio
authors.initials: N
authors.lastname: Kodama
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D002245:Carbon Dioxide / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D005974:Glutamate-Ammonia Ligase / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009584:Nitrogen / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D018756:GABA Antagonists; D011963:Receptors, GABA-A; D002245:Carbon Dioxide; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen