Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: Pathophysiology and potential therapeutic targets

Traumatic Brain Injury (TBI) is the most frequent cause of death and disability in young adults and children in the developed world, occurring in over 1.7 million persons and resulting in 50,000 deaths in the United States alone. The Centers for Disease Control and Prevention estimate that between 3.2 and 5.3 million persons in the United States live with a TBI-related disability, including several neurocognitive disorders and functional limitations. Following the primary mechanical injury in TBI, literature suggests the presence of a delayed secondary injury involving a variety of neuroinflammatory changes. In the hours to days following a TBI, several signaling molecules and metabolic derangements result in disruption of the blood-brain barrier, leading to an extravasation of immune cells and cerebral edema. The primary, sudden injury in TBI occurs as a direct result of impact and therefore cannot be treated, but the timeline and pathophysiology of the delayed, secondary injury allows for a window of possible therapeutic options. The goal of this review is to discuss the pathophysiology of the primary and delayed injury in TBI as well as present several preclinical studies that identify molecular targets in the potential treatment of TBI. Additionally, certain recent clinical trials are briefly discussed to demonstrate the current state of TBI investigation.