Role of innate inflammation in traumatic brain injury.

ABSTRACT

Traumatic brain injury is one of the leading causes of morbidity and mortality throughout the world. Its increasing incidence, in addition to its fundamental role in the development of neurodegenerative disease, proves especially concerning. Despite extensive preclinical and clinical studies, researchers have yet to identify a safe and effective neuroprotective strategy. Following brain trauma, secondary injury from molecular, metabolic, and cellular changes causes progressive cerebral tissue damage. Chronic neuroinflammation following traumatic brain injuries is a key player in the development of secondary injury. Targeting this phenomenon for development of effective neuroprotective therapies holds promise. This strategy warrants a concrete understanding of complex neuroinflammatory mechanisms. In this review, we discuss pathophysiological mechanisms such as the innate immune response, glial activation, blood-brain barrier disruption, activation of immune mediators, as well as biological markers of traumatic brain injury. We then review existing and emerging pharmacological therapies that target neuroinflammation to improve functional outcome.