Abstracts

Rationale: Whether long febrile seizures (FS) and febrile status epilepticus (FSE) cause temporal lobe epilepsy (TLE) has been unclear. In children, the majority of FS are simple and the outcomes of these seizures are benign. In contrast, up to 40% of children sustaining FSE may develop TLE. In an animal model of FSE, where other predisposing factors have been excluded, 45% of rats developed TLE. Thus, the model enables studying the mechanisms through which FSE may directly contribute to the onset of TLE. Inflammatory mechanisms are attractive candidates for contributing to the epileptogenic process that follows FSE: fever involves inflammation by definition, interleukin-1? (IL-1?) signaling was involved in the generation of FS, and hippocampal levels of IL-1? were augmented after FSE. Notably, hippocampal IL-1? levels remained high preferentially in FSE rats that became epileptic. An important mechanism by which inflammation contributes to the epileptogenic mechanism consists of blood-brain barrier (BBB) disruption (Ivens et al., 2007; Fabene et al., 2008). Therefore, here we tested if FSE alter the BBB permeability within hours and days after the seizures. Methods: Experimental FSE (30 minutes) was induced in rats on post-natal (P) day 10 (n = 10). To measure BBB leakage, we examined the extravasation of flueorescent albumin into the brain parenchyma. Experimental and control rats (n = 9) were perfused with fluorescein isothiocyanate (FITC)-tagged bovine albumin (10 mg/mL, 100mg/kg, 1 ml/min) in phosphate-buffered saline 24 hours after the seizures. After fixation in 4% paraformaldehyde for 48 hours, brains were cryoprotected and frozen. Frozen brains were cut into 20 ?m coronal sections, mounted on slides and albumin distribution visualized using fluorescence microscopy.Results: FITC-albumin extravasation into the parenchyma was detected in 6/8 rats that experienced FSE and in 2/9 control rats. Leakage was present in limbic structures (hippocampus, amygdala, entorhinal and piriform cortices), and hypothalamus in experimental rats. In control rats, FITC-albumin extravasation was detected in amygdala and hippocampus.Conclusions: FITC-albumin leakage arose in immature rats that experienced FSE as well as in controls. The fact that FITC-albumin was present outside the vasculature in the controls suggests that the BBB may not be fully mature at this age. The significantly increased number of FSE rats with albumin extravasation compared with controls (Fisher s exact test, p=0.05), suggests that inflammatory processes might interact with BBB immaturity to allow augmented albumin extravasation after the seizures. Current studies are focusing on the significance and predictive values of the BBB permeability changes after FSE will be examined. Supported by NIH NS35439. Ivens S, Kaufer D, Flores LP, Bechmann I, et al. Brain, 2007 130:535-547. Fabene PF, Navarro Mora G, Martinello M, Rossi B, et al. Nat Med, 2008 14:1377-1383.