title: Rapid, Coordinate Inflammatory Responses after Experimental Febrile Status Epilepticus: Implications for Epileptogenesis.
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 epilepsy-predictive 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.
authors.affiliation: Department of Anatomy/Neurobiology, University of California-Irvine , Irvine, California 92697.
authors.forename: Katelin P
authors.initials: KP
authors.lastname: Patterson
authors.affiliation: Department of Pediatrics, University of California-Irvine , Irvine, California 92697.
authors.forename: Gary P
authors.identifier: 0000-0002-4262-0481
authors.initials: GP
authors.lastname: Brennan
authors.affiliation: Department of Anatomy/Neurobiology, University of California-Irvine , Irvine, California 92697.
authors.forename: Megan
authors.identifier: 0000-0003-3240-8310
authors.initials: M
authors.lastname: Curran
authors.affiliation: Department of Pediatrics, University of California-Irvine, Irvine, California 92697; Department of Radiation Medicine and Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California 92350.
authors.forename: Eli
authors.initials: E
authors.lastname: Kinney-Lang
authors.affiliation: Department of Pediatrics, University of California-Irvine , Irvine, California 92697.
authors.forename: Celine
authors.initials: C
authors.lastname: Dubé
authors.affiliation: Department of Radiation Medicine and Department of Pediatrics, Loma Linda University School of Medicine , Loma Linda, California 92350.
authors.forename: Faisal
authors.initials: F
authors.lastname: Rashid
authors.affiliation: Department of Anatomy/Neurobiology, University of California-Irvine , Irvine, California 92697.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ly
authors.affiliation: Department of Radiation Medicine and Department of Pediatrics, Loma Linda University School of Medicine , Loma Linda, California 92350.
authors.forename: Andre
authors.initials: A
authors.lastname: Obenaus
authors.affiliation: Department of Anatomy/Neurobiology, University of California-Irvine, Irvine, California 92697; Department of Pediatrics, University of California-Irvine, Irvine, California 92697; Department of Neurology, University of California-Irvine, Irvine, California 92697.
authors.forename: Tallie Z
authors.initials: TZ
authors.lastname: Baram
mesh_terms: D000679:Amygdala / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000473:pathology; D015153:Blotting, Western; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D006624:Hippocampus / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000276:immunology* / Q000473:pathology; D013226:Status Epilepticus / Q000276:immunology* / Q000473:pathology
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D012333:RNA, Messenger
keywords: biomarker; cytokine; epilepsy; febrile seizures; heterogeneity; magnetic resonance imaging