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.
Highlights
Post-traumatic epilepsy (PTE) is a common long-term consequence of traumatic brain injury (TBI), for which there are few effective therapies
Inhibition of prostaglandin receptor EP2 reduces cytokine expression, markers of astrogliosis and microgliosis, mortality, hippocampal neurodegeneration, and blood–brain barrier (BBB) leakage in pilocarpine-treated mice in the absence of acute anticonvulsant effects (Jiang et al, 2012, 2013). These results, the long-term development of spontaneous seizures observed with over-expression of IL-6 and TNF-α indicate a role for cytokines in epileptogenesis that needs to be assessed in models of PTE
SUMMARY The development of medically intractable epilepsy is one of the most common long-term health problems associated with head injury in humans
Summary
Post-traumatic epilepsy (PTE) is a common long-term consequence of traumatic brain injury (TBI), for which there are few effective therapies. We review experimental animal models used in PTE research, including the neurophysiological and structural abnormalities believed to underlie the increased propensity of the injured brain to generate spontaneous seizures.
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