Traumatic brain injury and the effects of diazepam,diltiazem,and MK-801 on GABA-A receptor subunit expression in rat hippocampus

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 1,2,3,5,3,and 2 at 3 h,6 h,24 h,and 7 days post-injuy. 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 1,2,3,and 2,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 2 or 5 subunits at any time point post-injury. significant time-dependent changes in 1,3,3,and 2 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. © 2010 gibson et al; licensee biomed central ltd.