A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection

Abstract

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP.

The systemDrive: a Multisite, Multiregion Microdrive with Independent Drive Axis Angling for Chronic Multimodal Systems Neuroscience Recordings in Freely Behaving Animals

“…A multimodal setup like the one used in the current study would be ideal for the chronic observation of thalamocortical networks thought to be responsible for absence seizures in models of epilepsy (Pearce et al, 2014; Taylor et al, 2017) and the mechanisms relating spike-wave discharges in ictal-like thalamocortical dynamics and sleep (Shaw, 2004; Dewolfe et al, 2013). Other sensor modalities, such as cardiac and respiratory electrodes, and oxygen sensors, could be added to study the relationship between seizures and sudden unexpected death from epilepsy (Ssentongo et al, 2017; Bahari et al, 2018).…”

An EEG Experimental Study Evaluating the Performance of Texas Instruments ADS1299

“…These include testing 3D printed electrodes [ 2 ], ultra high impedance active electrodes [ 3 ], finger-based dry electrodes [ 4 ], and artefact rejection algorithms [ 5 , 6 ]. It has also been used in EEG experimental research to study neurophysiology in both humans [ 7 , 8 , 9 , 10 ] and mice [ 11 ]. Importantly, these studies are making decisions about the relative merits of these technologies and experimental outcomes based on parameters of the EEG recorded with the ADS1299.…”

Scurrying to Understand Sudden Expected Death in Epilepsy: Insights From Animal Models

“…These rats show an increased basal systolic arterial pressure and heart rate, and the major causes of death are dysautonomia and cardiac dysfunction. 58,59 In a murine model of postinfection-acquired epilepsy which has an SUDEP phenotype, 71 cardiac arrhythmia is preceded by abnormal cortical discharges, and this brain-heart interaction can be detected weeks before the first seizure onset, 60 supporting the idea that cardiac abnormalities originate in the brain.…”