This study establishes a foundation for continued study on the superior colliculus to ultimately develop preventative approaches for SUDEP.

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CURE Epilepsy Discovery: Investigating Spreading Depolarization in SUDEP

Key Points:
* Dr. Stuart Cain’s CURE Epilepsy Taking Flight Award ([link removed]) received while at the University of British Columbia, explored the mechanisms underlying Sudden Unexpected Death in Epilepsy (SUDEP).
* SUDEP occurs when the heart and respiration both stop in a process called “cardiorespiratory arrest.” An area of the brain called the brainstem ([link removed]) is critical in maintaining both heart function and respiration and is, therefore, an important brain area for researchers to study in order to understand the biological process through which SUDEP occurs. The brainstem is also connected to areas called the superior and inferior colliculus.
* A phenomenon known as “spreading depolarization” is known to contribute to respiratory arrest. Dr. Cain’s team investigated mechanisms underlying spreading depolarization in the areas of the brain connected to the brain stem called the superior and inferior colliculus.
* This study establishes a foundation for continued study on the superior colliculus to ultimately develop preventative approaches for SUDEP.

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Deep Dive:

Sudden Unexpected Death in Epilepsy (SUDEP) is one of the most tragic consequences of epilepsy. SUDEP occurs when a seemingly healthy person with epilepsy dies unexpectedly for no known reason. The biological causes of SUDEP are still not fully understood [1, 2]. Research suggests that SUDEP occurs because of the effects of seizures on the cardiovascular and respiratory systems resulting in “cardiorespiratory arrest”. Given that the brainstem is the part of the brain that controls heart rate and respiration, scientists have investigated the role of this region of the brain in causing SUDEP [3]. One phenomenon that has emerged as a possible explanation for SUDEP is called “spreading depolarization.” Spreading depolarization can be described as a wave of abnormal brain activity that travels through the layers of the brain in an organized fashion. Earlier work done by Dr. Cain and other researchers showed that spreading depolarization that engages the brainstem can be fatal. They also observed
that additional areas in the brain called the superior and inferior colliculus are susceptible to spreading depolarization, but only during seizures, and that spreading depolarization that traveled into the brainstem during seizures was fatal [4].

Past research studies have shown that the superior and inferior colliculus may be involved in epilepsy [5]. Dr. Cain’s research, funded by the CURE Epilepsy Taking Flight Award, sought to investigate if the superior and inferior colliculus may play a role in spreading depolarization to the brainstem [6]. In this study, Dr. Cain’s team used a genetic mouse model that is susceptible to seizures and SUDEP and has been previously shown to be a good model to understand activity in the brainstem during fatal seizures [4]. The team did several experiments using these mice, called Cacna1a^S218L mice, and state-of-the-art techniques. Using these techniques, Dr. Cain’s team first showed that when they stimulated the superior or the inferior colliculus, the mice experienced severe seizures, interrupted breathing (respiratory depression), and ultimately, death. Stimulation of the superior or the inferior colliculus started a wave of spreading depolarization that reached the brainstem in
Cacna1a^S218L mice, but not in normal mice.
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