Spreading depolarization: A phenomenon in the brain

In 1944, the physiologist Leão while studying epilepsy in the rabbit noticed a sudden temporary cessation of electrocorticographic (ECoG) activity accompanied with a large negative slow potential change recorded by extracellular electrodes, that is later known as spreading depolarizations (SDs). The depression of the brain electrical activity was slowly propagating through the cerebral cortex. The mechanism of propagation is still controversial. SDs and seizures are following each other interchangeably, yet the puzzle needs more investigation to be clarified. SDs have an obvious effect on blood-brain barrier integrity mainly through transcellular and paracellular routs, but not much known about that especially following traumatic brain injury (TBI). The cortical spreading depolarization (CSD) and the depression of brain activity have been recognized following a variety of neurological diseases and brain injuries. CSD has been studied in animal models and recently in humans, and it has been recognized and described as a massive neuronal depolarization accompanied with high level of disturbances in transmembrane ion gradients and significant changes in cerebral blood flow (1-3). Although there is a considerable amount of literatures on SD have been done since 1944, but the biophysical mechanism of SD, the long term effect on the brain structures and functions, and it is role in different disorders are still incompletely understood.Here, we summarize the history of spreading depolarization and the most accepted hypothesis for mechanism of initiation and propagation of that phenomenon. Most importantly, we present the most updated research on the relationship and interaction between spreading depolarization and traumatic brain injuries, seizure, blood-brain barrier, neurovascular coupling, and other neurological conditions. Learning more about the spreading depolarization will increase our understanding about that phenomenon and may explain its association with different clinical presentations.