title: Traumatic brain injury induces rapid enhancement of cortical excitability in juvenile rats.
abstract: OBJECTIVE
  Following a traumatic brain injury (TBI), 5-50% of patients will develop posttraumatic epilepsy (PTE) with children being particularly susceptible. Currently, PTE cannot be prevented and there is limited understanding of the underlying epileptogenic mechanisms. We hypothesize that early after TBI the brain undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes the development of epilepsy.
  
  
  METHODS
  To examine the effect of pediatric TBI on cortical excitability, we performed controlled cortical impact (CCI) on juvenile rats (postnatal day 17). Following CCI, animals were monitored for the presence of epileptiform activity by continuous in vivo electroencephalography (EEG) and/or sacrificed for in vitro whole-cell patch-clamp recordings.
  
  
  RESULTS
  Following a short latent period, all animals subjected to CCI developed spontaneous recurrent epileptiform activity within 14 days. Whole-cell patch-clamp recordings of layer V pyramidal neurons showed no changes in intrinsic excitability or spontaneous excitatory postsynaptic currents (sEPSCs) properties. However, the decay of spontaneous inhibitory postsynaptic currents (sIPSCs) was significantly increased. In addition, CCI induced over a 300% increase in excitatory and inhibitory synaptic bursting. Synaptic bursting was prevented by blockade of Na(+)-dependent action potentials or select antagonism of glutamate or GABA-A receptors, respectively.
  
  
  CONCLUSIONS
  Our results demonstrate that CCI in juvenile rats rapidly induces epileptiform activity and enhanced cortical synaptic bursting. Detection of epileptiform activity early after injury suggests it may be an important pathophysiological component and potential indicator of developing PTE.
authors.affiliation: University of Arizona, College of Medicine - Phoenix, Phoenix, AZ, USA; School of Life Sciences, Arizona State University, Phoenix, AZ, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Nichols
authors.forename: Roxy
authors.initials: R
authors.lastname: Perez
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
authors.forename: Trent
authors.initials: T
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology* / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine
keywords: Cerebral cortex; Epilepsy; Neurophysiology; Synaptic plasticity; Traumatic brain injury