title: Traumatic brain injury and the effects of diazepam, diltiazem, and MK-801 on GABA-A receptor subunit expression in rat hippocampus.
abstract: BACKGROUND
  Excitatory amino acid release and subsequent biochemical cascades following traumatic brain injury (TBI) have been well documented, especially glutamate-related excitotoxicity. The effects of TBI on the essential functions of inhibitory GABA-A receptors, however, are poorly understood.
  
  
  METHODS
  We used Western blot procedures to test whether in vivo TBI in rat altered the protein expression of hippocampal GABA-A receptor subunits alpha1, alpha2, alpha3, alpha5, beta3, and gamma2 at 3 h, 6 h, 24 h, and 7 days post-injury. We then used pre-injury injections of MK-801 to block calcium influx through the NMDA receptor, diltiazem to block L-type voltage-gated calcium influx, or diazepam to enhance chloride conductance, and re-examined the protein expressions of alpha1, alpha2, alpha3, and gamma2, all of which were altered by TBI in the first study and all of which are important constituents in benzodiazepine-sensitive GABA-A receptors.
  
  
  RESULTS
  Western blot analysis revealed no injury-induced alterations in protein expression for GABA-A receptor alpha2 or alpha5 subunits at any time point post-injury. Significant time-dependent changes in alpha1, alpha3, beta3, and gamma2 protein expression. The pattern of alterations to GABA-A subunits was nearly identical after diltiazem and diazepam treatment, and MK-801 normalized expression of all subunits 24 hours post-TBI.
  
  
  CONCLUSIONS
  These studies are the first to demonstrate that GABA-A receptor subunit expression is altered by TBI in vivo, and these alterations may be driven by calcium-mediated cascades in hippocampal neurons. Changes in GABA-A receptors in the hippocampus after TBI may have far-reaching consequences considering their essential importance in maintaining inhibitory balance and their extensive impact on neuronal function.
authors.affiliation: Department of Psychology, Washington College, Chestertown, MD 21620, USA. cgibson2@washcoll.edu
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Gibson
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Meyer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hamm
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D002121:Calcium Channel Blockers; D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D021122:Protein Subunits; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D004110:Diltiazem; D003975:Diazepam