Concussion: pathophysiology and clinical translation

Abstract

The majority of the 3.8 million estimated annual traumatic brain injuries (TBI) in the United States are mild TBIs, or concussions, and they occur primarily in adolescents and young adults. A concussion is a brain injury associated with rapid brain movement and characteristic clinical symptoms, with no associated objective biomarkers or overt pathologic brain changes, thereby making it difficult to diagnose by neuroimaging or other objective diagnostic tests. Most concussion symptoms are transient and resolve within 1-2 weeks. Concussions share similar acute pathophysiologic perturbations to more severe TBI: there is a rapid release of neurotransmitters, which causes ionic disequilibrium across neuronal membranes. Re-establishing ionic homeostasis consumes energy and leads to dynamic changes in cerebral glucose uptake. The magnitude and duration of these changes are related to injury severity, with milder injuries showing faster normalization. Cerebral sex differences add further variation to concussion manifestation. Relative to the male brain, the female brain has higher overall cerebral blood flow, and demonstrates regional differences in glucose metabolism, inflammatory responses, and connectivity. Understanding the pathophysiology and clinical translation of concussion can move research towards management paradigms that will minimize the risk for prolonged recovery and repeat injury.

Keywords: axonal damage; biomarkers; cognition; energy crisis; headache; inflammation; pathophysiology; reaction time; spreading depression.