RT Journal Article
SR Electronic
T1 Epileptogenesis Provoked by Prolonged Experimental Febrile Seizures: Mechanisms and Biomarkers
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7484
OP 7494
DO 10.1523/JNEUROSCI.0551-10.2010
VO 30
IS 22
A1 Dubé, Céline M.
A1 Ravizza, Teresa
A1 Hamamura, Mark
A1 Zha, Qinqin
A1 Keebaugh, Andrew
A1 Fok, Kimberly
A1 Andres, Adrienne L.
A1 Nalcioglu, Orhan
A1 Obenaus, Andre
A1 Vezzani, Annamaria
A1 Baram, Tallie Z.
YR 2010
UL http://www.jneurosci.org/content/30/22/7484.abstract
AB Whether long febrile seizures (FSs) can cause epilepsy in the absence of genetic or acquired predisposing factors is unclear. Having established causality between long FSs and limbic epilepsy in an animal model, we studied here if the duration of the inciting FSs influenced the probability of developing subsequent epilepsy and the severity of the spontaneous seizures. We evaluated if interictal epileptifom activity and/or elevation of hippocampal T2 signal on magnetic resonance image (MRI) provided predictive biomarkers for epileptogenesis, and if the inflammatory mediator interleukin-1β (IL-1β), an intrinsic element of FS generation, contributed also to subsequent epileptogenesis. We found that febrile status epilepticus, lasting an average of 64 min, increased the severity and duration of subsequent spontaneous seizures compared with FSs averaging 24 min. Interictal activity in rats sustaining febrile status epilepticus was also significantly longer and more robust, and correlated with the presence of hippocampal T2 changes in individual rats. Neither T2 changes nor interictal activity predicted epileptogenesis. Hippocampal levels of IL-1β were significantly higher for >24 h after prolonged FSs. Chronically, IL-1β levels were elevated only in rats developing spontaneous limbic seizures after febrile status epilepticus, consistent with a role for this inflammatory mediator in epileptogenesis. Establishing seizure duration as an important determinant in epileptogenesis and defining the predictive roles of interictal activity, MRI, and inflammatory processes are of paramount importance to the clinical understanding of the outcome of FSs, the most common neurological insult in infants and children.