S144 Cortical spreading depression, relevance to migraine and acute brain injury in humans, and new mechanisms

Abstract

Cortical spreading depression/depolarization (CSD) is a depolarization wave in cerebral gray matter that propagates across the brain at slow velocity, 2–5 mm/min. For many years it was believed that CSD was an artifact produced in animal experiments and without clinical relevance. In the 1980s, brain scans of cerebral blood flow (CBF) in patients during migraine showed what was termed a ‘spreading oligemia’, a wave of reduced blood flow that propagated across the brain at the same rate and with the same signs of vascular impairment as CSD. These studies led to the view that CSD triggers migraine, and that CSD is a benign phenomenon in normal human brains with preserved perfusion and energy metabolism. A new research field in translational neuroscience has opened as a result of the recognition since 2002 that CSD can be detected in many patients with acute brain injury, whether vascular and spontaneous, or traumatic in origin as well. In this review lecture, I trace CSD from the first description in rabbits through to their detection and study in migraine and the injured human brain, and the evolution of understanding of the importance of spread of mass depolarizations in cerebral grey matter. Recognition of the likely fundamental significance of CSD for this wide range of serious acute encephalopathies in humans provides a powerful case for a fresh examination of neuroprotection strategies.