Seizures and Interictal Epileptiform Activity in the Rat Collagenase Model for Intracerebral Hemorrhage.

Charlotte Germonpré,Veerle De Herdt,Paul Boon,Silke Proesmans,Charlotte Bouckaert,Robrecht Raedt,Mathieu Sprengers

doi:10.3389/fnins.2021.682036

Abstract

AimsIntracerebral hemorrhage (ICH) is a known risk factor for the development of acute symptomatic as well as late unprovoked seizures. The underlying pathophysiology of post-ICH seizures is incompletely understood and there are no reliable predictive biomarkers. An animal model to study post-ICH seizures is currently lacking. The aim of this study was to investigate (1) the occurrence of seizures and interictal epileptiform activity in the ICH rat collagenase model using long-term video-EEG monitoring (VEM) and (2) whether seizure occurrence was associated with interictal epileptiform activity and histological features.MethodsMale Sprague-Dawley rats were implanted with epidural electrodes. After 1 week of baseline VEM, collagenase was injected in left striatum to induce an ICH. VEM was continued for 180 days to assess the occurrence of post-ICH seizures and interictal epileptiform activity (spikes and epileptiform discharges). At the end of the experiment, animals were euthanized for histological characterization of the hemorrhagic lesion, using cresyl violet, Prussian blue and immunofluorescence staining.ResultsAcute symptomatic seizures occurred in 4/12 animals between 46 and 80 h after ICH induction. Late unprovoked seizures were present in 2/12 animals and started at 90 and 103 days post-ICH. Animals with late unprovoked seizures did not have acute symptomatic seizures. All electrographic seizures were accompanied by clear behavioral changes. Interictal spikes and epileptiform discharges were observed in all animals but occurred more frequently in rats with late seizures (p = 0.019 and p < 0.001, respectively). Animals with acute symptomatic seizures had more extended hemorrhagic lesions and hemosiderin deposits in the piriform cortex.ConclusionBoth acute symptomatic and late unprovoked seizures were observed in the rat collagenase model. Interictal epileptiform activity was more frequently seen in animals with late seizures. Rats with acute symptomatic seizures showed more extensive lesions and hemosiderin deposits in the piriform cortex. This model could be used to further explore possible biomarkers for epileptogenesis.

Highlights

Spontaneous non-traumatic intracerebral hemorrhage (ICH) is the second most common type of stroke, after ischemic stroke, and occurs in 10–20% of all stroke patients
The late seizures lasted for 83 ± 17 s and they were all accompanied by behavioral changes with a median Racine score of 4.5
The small number of animals with late seizures prevented us from making strong conclusions about the association between lesion volume or glial markers and the occurrence of seizures but we found that animals with late seizures presented more often with interictal epileptiform activity and rats with acute symptomatic seizures showed more extensive lesions and hemosiderin deposits in the piriform cortex

Summary

Introduction

Spontaneous non-traumatic intracerebral hemorrhage (ICH) is the second most common type of stroke, after ischemic stroke, and occurs in 10–20% of all stroke patients. It is a devastating acute cerebrovascular disorder with high mortality and morbidity. Acute symptomatic seizures are distinguished from late or unprovoked seizures, which occur later than 7 days post-stroke This type of seizures is referred to as post-stroke epilepsy and has a reported incidence of up to 10%, with a median time to first seizure of 6–9 months post-ICH (Rossi et al, 2013; Haapaniemi et al, 2014)

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