AIMS: 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. CONCLUSION: 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.
AIMS: 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. CONCLUSION: 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: Eric M Casella; Theresa Currier Thomas; Dana L Vanino; Wendy Fellows-Mayle; Jonathan Lifshitz; J Patrick Card; P David Adelson Journal: Childs Nerv Syst Date: 2014-06-01 Impact factor: 1.475
Authors: D H Smith; H D Soares; J S Pierce; K G Perlman; K E Saatman; D F Meaney; C E Dixon; T K McIntosh Journal: J Neurotrauma Date: 1995-04 Impact factor: 5.269
Authors: Stephanie S Sloley; Bevan S Main; Charisse N Winston; Alex C Harvey; Alice Kaganovich; Holly T Korthas; Adam P Caccavano; David N Zapple; Jian-Young Wu; John G Partridge; Mark R Cookson; Stefano Vicini; Mark P Burns Journal: Nat Commun Date: 2021-05-10 Impact factor: 14.919