 Since their first description in 1944, spreading depolarizations SDs were subsequently demonstrated in numerous animal studies as a mechanism of secondary brain injury after ischemic stroke, subarachnoid hemorrhage SAH, and traumatic brain injury. SDs have also been demonstrated to occur in the cerebral grey matter of the human brain in patients after acute brain injuries such as TBI, SAH, and ischemic stroke. To date, electrocorticography ECoG monitoring of over 500 patients after TBI has shown that SDs occur in 55-90 of individuals for days to weeks after the initial injury. These studies have demonstrated an initial peak in SD frequency at 1-2 days post-TBI and a second peak at 6-7 days. Furthermore, SDs are associated with worse outcomes after TBI. 