The long-term effects of limbic non-convulsive status epilepticus in peri-adolescent rats

Abstract

To optimize the clinical approach to non-convulsive status epilepticus (NCSE), it is essential to gain insight into its long-term effects on cognition and behaviors. Here, we investigated limbic NCSE-induced hippocampal injury and behavioral deficits in peri-adolescent rats. NCSE was induced in P43 Sprague Dawley rats with intrahippocampal subconvulsive doses of kainic acid (NCSE group, n = 14) under continuous epidural cortical electroencephalography (EEG). Controls received volume-matched saline (n = 18). Following one month of continuous EEG monitoring, rats were sequentially subjected (P73-91) to the open field, the Morris water maze (MWM), and the modified two-way active avoidance (MAAV). Rats were sacrificed at P91 to histologically assess hippocampal injury with NeuN (neuronal nuclei) staining, levels of GFAP (glial fibrillary acidic protein), and synaptophysin (Syp). Following kainic acid administration, the NCSE group experienced electroclinical seizures characterized by behavioral arrest and oromotor automatisms without tonic-clonic activity (latency: 15.93 ± 4.70 min, duration: 68.35 ± 17.97 min). There were no seizure recurrences in the rest of the long-term recordings. Compared to controls, NCSE rats had impaired place learning in the MWM, and lower rates of context-cued shock avoidance in the MAAV (p < 0.05). The NCSE and control groups had comparable hippocampal neuronal densities and GFAP levels, but NCSE rats had significantly lower hilar Syp levels. One episode of limbic NCSE during peri-adolescence results in later life hippocampal synaptic dysfunction and contextual learning deficits. These data suggest that the diagnosis and treatment of NCSE should be prompt.