Spreading Depression: Mechanism of Action in Neuroinflammatory Diseases

Spreading Depression (SD) is a pathophysiological phenomenon that occurs as a transient wave of depolarization of neurons and glial cells, and results in a temporary suppression of the activity of neurons. In this phenomenon, there is a disturbance in the distribution and balance of ions between the extracellular and intracellular environments and in cellular metabolism. Furthermore, SD is accompanied by a short increase in bioelectrical activity, followed by a strong transient depression of neuronal activity and a long-term excitability of the neuronal network. Recently, the neuroinflammatory function of this phenomenon, as one of the main contributors to neurological diseases, has been widely investigated. The role of SD has been revealed in some neurological diseases, such as migraine with aura, epilepsy, transient global amnesia, and cerebrovascular diseases, including cerebral ischemia-infarction and stroke, as well as intracranial hemorrhage caused by traumatic head injury.

Despite the large and growing body of evidence, the exact mechanism of SD propagation is still not clear and requires more in-depth investigations. Therefore, in this review, we discuss the underlying mechanism of SD and highlight the role of SD in the development of neuroinflammatory diseases.