Rapid, coordinate inflammatory responses after experimental febrile status epilepticus: Implications for epileptogenesis

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Abstract

Epilepsy is a common neurological disorder with many causes. For temporal lobe epilepsy, antecedent insults are typically found. These risk factors include trauma or history of long fever-associated seizures (febrile status epilepticus) in childhood. Whereas the mechanisms by which such insults promote temporal lobe epilepsy are unknown, an extensive body of work has implicated inflammation and inflammatory mediators in both human and animal models of the disorder. However, direct evidence for an epileptogenic role for inflammation is lacking. Here we capitalized on a model where only a subgroup of insult-experiencing rodents develops epilepsy. We reasoned that if inflammation was important for generating epilepsy, then early inflammation should be more prominent in individuals destined to become epileptic compared with those that will not become epileptic. In addition, the molecular and temporal profile of inflammatory mediators would provide insights into which inflammatory pathways might be involved in the disease process. We examined inflammatory profiles in hippocampus and amygdala of individual rats and correlated them with a concurrent noninvasive, amygdalar magnetic resonance imaging epilepsy-predictive marker. We found significant individual variability in the expression of several important inflammatory mediators, but not in others. Of interest, a higher expression of a subset of hippocampal and amygdalar inflammatory markers within the first few hours following an insult correlated with the epilepsypredictive signal. These findings suggest that some components of the inflammatory gene network might contribute to the process by which insults promote the development of temporal lobe epilepsy.

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Patterson, K. P., Brennan, G. P., Curran, M., Kinney-Lang, E., Dubé, C., Rashid, F., … Baram, T. Z. (2015). Rapid, coordinate inflammatory responses after experimental febrile status epilepticus: Implications for epileptogenesis. ENeuro, 2(5). https://doi.org/10.1523/ENEURO.0034-15.2015

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