CORTICAL SPREADING DEPOLARISATION IN NEUROLOGICAL DISEASE – AN INTRODUCTION By Toby Jeffcote Cortical spreading depolarization (CSD) is a spreading loss of ion homeostasis, altered vascular response, change in synaptic architecture, and subsequent depression in electrical activity following an inciting neurological injury. It was first described by Leão in 1944, a disturbance in neuronal electrophysiology has since been demonstrated in a number of animal studies, and recently a few human studies that examine the occurrence of this depolarizing phenomenon in the setting of a variety of pathological states, including migraines, cerebrovascular accidents, epilepsy, intracranial hemorrhages, and traumatic brain injuries. The onset of CSD has been demonstrated experimentally following a disruption in the neuronal environment leading to glutamate-induced toxicity. This initial event leads to pathological changes in the activity of ion channels that maintain membrane potential. Recovery mechanisms such as sodium-potassium pumps that aim to restore homeostasis fail, leading to osmolar shifts of fluid, swelling of the neuron, and ultimately a measurable depression in cortical activity that spreads in the order of millimeters per minute. Equally important is the resulting change in vascular response. In healthy tissue, increased electrical activity is coupled with release of vasodilatory factors such as nitric oxide and arachidonic acid metabolites that increase local blood flow to meet increased energy expenditure. In damaged tissue, not only is the restorative vascular response lacking but a vasoconstrictive response is promoted and the ischemia that follows adds to the severity of the initial injury. Tissue threatened by this ischemic response is then at elevated risk for CSD propagation and falls into a vicious cycle of electrical and hemodynamic disturbance. Efforts have been made to halt this spreading cortical depression using N-methyl-D-aspartate receptor antagonists and other ion channel blockers to minimize the damaging effects of CSD that can persist long after the triggering insult.

1. Cortical spreading depolarisation
and neurological disease
CORTICAL SPREADING
DEPOLARISATION IN
NEUROLOGICAL DISEASE – AN
INTRODUCTION
BY TOBY JEFFCOTE

2. Migraine aura
DIND in SAH
Expansion of
ischaemic stroke
Secondary brain
injury in TBI
CSD

3. Aristides Leao

4. CSD in humans

5. Interpreting the ECoG

6. Mechanism of CSD

7. Stroke and the CSD continuum
Infarct core
Inner penumbra
Outer penumbra
Normal perfusion

10. N = 109
CSD in 56%

12. Future research
Pre-clinical studies
Therapeutic studies
Clinical detection
studies
CSD

13. Cortical spreading depolarisation
and neurological disease
CORTICAL SPREADING
DEPOLARISATION IN
NEUROLOGICAL DISEASE – AN
INTRODUCTION
BY TOBY JEFFCOTE