Cortical Spreading Depression in the Setting of Traumatic Brain Injury

Cortical spreading depression (CSD) is a pathophysiologic phenomenon that describes an expanding wave of depolarization within the cortical gray matter. Originally described over 70 years ago, this spreading depression disrupts neuronal and glial ionic equilibrium, leading to increased energy demands that can cause a metabolic crisis. This results in secondary insult, further perpetuating brain injury and neuronal death. Initially not thought to be of clinical significance, the view of CSD was modified with the advent of intracranial electroencephalography, or electrocorticography. With these improved monitoring techniques, CSD has been identified as a major mechanism by which traumatic brain injury (TBI) imparts its negative sequalae. TBI is a heterogenous disease process that runs the gamut of clinical presentations. This includes concussion, epidural and subdural hematoma, diffuse axonal injury, and subarachnoid hemorrhage. Nonetheless, CSD appears to be frequently occurring among the various types of TBI, thus allowing for the potential development of targeted therapies in an otherwise ill-fated patient cohort. Although a complete understanding of the interplay between CSD and TBI has not yet been achieved, the authors recount the efforts that have been employed over the last several decades in an effort to bridge this gap. In addition, our current understanding of the role neuroimmune cells play in CSD is discussed in the context of TBI. Finally, current therapeutic strategies using CSD as a pharmacologic target are explored with respect to their clinical use in patients with TBI.