Illuminating spreading depolarization: mechanisms, consequences & therapeutic targets

Abstract

This thesis examines the role of spreading depolarization (SD) in the development of migraine and epilepsy, with a focus on familial hemiplegic migraine type 1 (FHM1). FHM1 is a genetic disorder associated with increased neuronal activity and can lead to sudden unexpected death in epilepsy (SUDEP). The studies described in this thesis used mouse models with specific genetic mutations in the FHM1 gene that lead to increased neuronal activity, thereby increasing the risk of epileptic seizures and fatal complications.

Several studies in this thesis employed optogenetics, a technique that uses light to stimulate cells in the brain. Using optogenetics, SD was induced in the brains of living mice to study the subsequent effects. This has led to new insights into how SD contributes to the development of epileptic seizures and migraines. Other chapters focus on therapeutic targets for migraine. For example, the effects of endocannabinoids were investigated, which may offer therapeutic benefits. Changes in the blood plasma of mice were also analyzed to identify molecular biomarkers that could assist in developing new treatments for migraines.

The findings highlight the complexity of the disease processes behind migraine and epilepsy and provide new insights for future therapies.