A novel peri-adolescent model of hippocampal Non-Convulsive Status Epilepticus : Evidence of early alterations in synaptic plasticity and cognitive and emotional behaviors

Abstract

Background: Seizures consist of paroxysmal synchronous neuronal firing that may result in various signs and symptoms such as involuntary movements, abnormal sensations, and behavioral changes. While prolonged seizures accompanied by rhythmic clonic and-or tonic muscle stiffening (convulsions), termed convulsive status epilepticus, are known to be associated with mortality, brain damage, and chronic cognitive and psychiatric deficits, the effect of the non-convulsive type of status epilepticus (NCSE) on the brain remains largely unknown. Moreover, in current practice, the treatment approach to NCSE is less emergent compared to its convulsive counterpart, and its diagnosis is made relatively late, usually following multiple, often behaviorally subtle, episodes. This seemingly benign clinically non-dramatic condition has lately been the subject of few but alarming preclinical and clinical reports, suggesting NCSE-related brain damage, in addition to cognitive and emotional behavioral deficits. Confirming such potential detrimental consequences is highly clinically relevant. If NCSE has such major harmful sequealae, it should be diagnosed and treated more urgently, since in current clinical practice, it is considered less urgent than CSE. While much insight about CSE has been gained from animal models, expanding our knowledge about NCSE has been hindered by the lack of well-established animal models. Given that the temporal lobe is one of the most common sites of NCSE, here we propose to electroclinically validate a novel model of peri-adolescent hippocampal NCSE. Through this model, we aim at investigating potential cognitive, emotional-behavioral changes, as well as alterations in hippocampal structure and in synaptic plasticity markers, namely synaptophysin (Syp) and activity-related cytoskeletal (Arc) protein, following one or two episodes of NCSE, in this likely underdiagnosed condition that is usually brought to medical attention following multiple occurrences. Methods: Postnatal day 43 (P43) rats received