title: Neural circuit mechanisms of post-traumatic epilepsy.
abstract: Traumatic brain injury (TBI) greatly increases the risk for a number of mental health problems and is one of the most common causes of medically intractable epilepsy in humans. Several models of TBI have been developed to investigate the relationship between trauma, seizures, and epilepsy-related changes in neural circuit function. These studies have shown that the brain initiates immediate neuronal and glial responses following an injury, usually leading to significant cell loss in areas of the injured brain. Over time, long-term changes in the organization of neural circuits, particularly in neocortex and hippocampus, lead to an imbalance between excitatory and inhibitory neurotransmission and increased risk for spontaneous seizures. These include alterations to inhibitory interneurons and formation of new, excessive recurrent excitatory synaptic connectivity. Here, we review in vivo models of TBI as well as key cellular mechanisms of synaptic reorganization associated with post-traumatic epilepsy (PTE). The potential role of inflammation and increased blood-brain barrier permeability in the pathophysiology of PTE is also discussed. A better understanding of mechanisms that promote the generation of epileptic activity versus those that promote compensatory brain repair and functional recovery should aid development of successful new therapies for PTE.
authors.affiliation: Epilepsy Research Laboratory, Department of Neurological Surgery, University of California San Francisco, CA, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hunt
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Boychuk
authors.forename: Bret N
authors.initials: BN
authors.lastname: Smith
keywords: epilepsy; epileptogenesis; neuroinflammation; pilocarpine; seizures; synapse; traumatic brain injury