Abstracts

Rationale: Paediatric status epilepticus (SE) may result from acquired, metabolic, immune, genetic or unknown causes. We characterized an infantile rat model of de novo SE to study the pathologic sequelae ignited by unremitting seizures in the immature brain that include atrophy, cognitive deficits and epilepsy.  Methods: SE was induced by unilateral intra-amygdala injection of 2 μg kainic acid (KA) in cortical electrode-implanted postnatal day (P)13 male rat pups. Controls were injected with saline. Astrocytes and microglia activation and Fluoro-Jade-positive degenerating neurons were analyzed by immunohistochemistry and confocal microscopy; neuroinflammation and oxidative stress markers were measured by RTqPCR. Different cohorts of SE-exposed P13 rats were longitudinally video-EEG monitored, exposed to the Morris Water Maze to test learning and memory, and to T2-weighted MRI sequence to determine brain atrophy.  Results: EEG monitored convulsive SE was defined by the appearance of continuous spikes with a frequency >1.0 Hz and an amplitude at least 2.5-fold higher than the standard deviation of the baseline tracing. SE occurred 31.0 +- 2.3 min after KA injection and lasted for 3.5 +- 0.5 h (mean +- SEM, n=9). Epileptiform events of higher amplitude were recorded in the cortex ipsilateral to injected amygdala vs the contralateral homotypic area. Glia activation, induction of the ictogenic cytokines IL‐1β and TNF-a and HMGB1, oxidative stress markers were measured in rats (n=6-7 rats each group) from 2 h to 1 week post-SE. Degenerating neurons were detected in cortex, hippocampus, amydgala, striatum and reticular thalamic nucleus. Spontaneous recurrent seizures (3-5/week) developed around 1 month after SE in about 60% of rats as assessed by video-EEG recording for at least 5 months (n=19). SE was similar in onset, severity and duration in all animals. MRI showed progressive atrophy in cortical and subcortical regions starting before epilepsy onset. Rats displayed cognitive impairment after epilepsy onset denoting an encephalopathic effect of spontaneous seizures. Conclusions: This infantile SE rat model can be exploited for mechanistic studies, to test novel drugs and for developing biomarkers of disease onset and progression.Fonts of support: Ring14 International Onlus; European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n. _x0004_602102 (EPITARGET)  Funding: No funding