Bij hersenbeschadiging kunnen massale ontladingen van zenuwcellen ontstaan met als gevolg minder bloeddoorstroming. Dit onderzoek gaat na in hoeverre deze ontladingen schadelijk zijn in de acute fase van een beroerte en of door het remmen van deze ontladingen patiënten na een beroerte beter herstellen.
Stroke is one of the leading causes of death in the world. According to epidemiologic reports the overall incidence of stroke will rise dramatically because of the aging population and the increasing burden of obesity and diabetes. Migraine is a disabling disorder that affects 12% of adults and is characterised by severe headache attacks. In one third of patients headaches are preceded by neurological symptoms (aura). Stroke and migraine are closely connected. Migraine is an independent risk factor for stroke and is associated with subclinical infarcts. Understanding the stroke-migraine relationship will gain insight in both diseases. One intriguing shared pathophysiologic mechanism is spreading depression (SD). SD, the presumed underlying mechanism of a migraine aura, is a slowly progressing wave of depression (temporary loss of activity) of brain cells. In healthy persons SDs are relatively benign and often followed by an increase in cerebral blood flow. In experimentally damaged brain SD may lead to an inverse reaction causing decreased blood flow and eventually ischaemia. SDs are therefore often called killer waves . Recently it became clear that SD occurs not only in migraine but also in humans with stroke. In patients with ischaemic stroke SDs were found in the penumbra (border zone around the infarct that is at risk of infarction but not yet irreversibly injured) of the infarct. SDs were also detected after subarachnoid haemorrhage (SAH), an often lethal subset of stroke. Several days after SAH a mysterious detrimental phenomenon occurs when ischaemia develops in 30% of patients. The mechanism for this delayed cerebral ischaemia (DCI) is unclear. The exact role of SD in ischaemic stroke and DCI after SAH is unknown. The first aim of my project is to unravel the contribution of SD to the pathogenesis of ischaemic stroke and SAH. My second aim is to investigate the potential of new imaging techniques such as high field MRI and CT-perfusion to characterise SD in patients and rodents. My third aim is to explore possible new treatment strategies by assessing the beneficial effect of SD inhibitors in ischaemic stroke and SAH. This project combines data from large cohorts of well-characterised stroke patients with state-of-the-art imaging techniques and experimental migraine and stroke models and perfectly matches my background in basic science, neurology and epidemiology.