THE EFFECT OF NON-CONVULSIVE SEIZURE BURDEN ON COGNITION AND EMOTIONAL BEHAVIOR IN PERI-ADOLESCENT RATS

Abstract

Background: Non-Convulsive status epilepticus (NCSE) consists of prolonged seizures without tonic muscle stiffening or clonic rhythmic activity. In a clinical setting, NCSE is often underdiagnosed due to difficulties in recognizing its manifestations (altered consciousness, blanking, automatisms), and therefore it frequently recurs prior to coming to medical attention. Moreover, because the potential harmful effects of NCSE on the immature brain remain elusive, the urgency of its diagnosis and aggressivity of its treatment are controversial. Previous work in our laboratory revealed that NCSE in peri-adolescent rats is associated with an early hippocampal synaptic dysfunction and ensuing learning deficits. Aim: We aim at investigating whether these short-term harmful effects persist later in life leading to neurodevelopmental consequences and whether they are reinforced by recurrence. Methodology: One or two episodes of NCSE were induced via stereotaxically-delivered intrahippocampal kainic acid (KA) in peri-adolescent rats at post-natal day 42 (P42) under EEG monitoring (The LSK group received one KA injection while the LRK group received two injections. The LCTR group received saline injections). We performed behavioral tests (P72) for auditory and contextual learning (modified two-way active avoidance test), and visuospatial navigation and memory deficits (Morris water maze test). We also assessed emotional behaviors such as hyperactivity, exploratory and anxiety-like behaviors through open field and light dark tests, and depressive-like behaviors through the forced swim test. Continuous EEG monitoring was done for a duration of one month before behavioral testing and one week post behavioral tests. Potential hippocampal damage and synaptic dysfunction were assessed histologically via immunohistochemistry (neuronal counts and synaptophysin, respectively). Results: All induced seizures were of almost equal duration and latency between the rats. No seizure recurrence was detected. During the probe trial in the Morris water maze test, and as compared to the control group, the injured groups of rats spent less time in the probe quadrant, which shows visuospatial, memory, and retention deficits post NCSE. Conclusion: The preliminary data shows that NCSE causes visuospatial navigation and memory deficits. Knowing these harmful effects proves that further research should be done to start diagnosing and treating NCSE more timely and aggressively.