Excessive Neuronal Inhibition Changes Physiological Functions And Increases SUDEP Risk

Else Tolner, PhD - Arn Van Den Maagdenberg, PhD
Leiden University Medical Center (LUMC), the Netherlands

Risk factors and mechanisms for SUDEP are largely unknown. Our research will test the hypothesis that suppression of brain activity after a seizure reflects increased neuronal inhibition and is linked to fatal outcome. We will use transgenic migraine mouse models carrying human pathogenic Cacna1a gene mutations, that exhibit various neurological disease features including fatal seizures. We hypothesize that these seizures are explained by the known enhanced level of neuronal excitation in our mice and excessive neuronal inhibition. By experimentally modulating the misbalance between excitatory and inhibitory neuronal activity, e.g. using drugs that affect adenosinergic inhibition, we expect to aggravate or ameliorate the SUDEP phenotype in our mice. Thus we hope to provide a mechanistic understanding of SUDEP pathophysiology and development of diagnostic tools for identifying susceptible individuals.


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