Modulating factors for and consequences of cortical spreading depression

Abstract

The research in this thesis was aimed at identifying and understanding mechanisms underlying modulating factors for and consequences of cortical spreading depression (CSD), the pathophysiological substrate for migraine aura that occurs in one-third of migraine patients. In this thesis, experimental studies on CSD were performed in wild-type (WT) and transgenic migraine mice, which express CaV2.1 Ca2+ channels with a mutated _1 subunit that contains the R192Q missense mutation. The R192Q mutation was previously identified in patients with familial hemiplegic migraine type 1 (FHM1) and causes gain-of-function effects in terms of neuronal Ca2+ influx, neurotransmission, and susceptibility to experimentally induced CSD. Using various experimental strategies, in this thesis, the FHM1 R192Q mouse model was used to study pathophysiological mechanisms of the initiation and modulation of CSD as well as of neurobiological and molecular changes that accompany CSD events.