Concussion susceptibility is mediated by spreading depolarization-induced neurovascular dysfunction.

The mechanisms underlying the complications of mild traumatic brain injury, including post-concussion syndrome, post-impact catastrophic death, and delayed neurodegeneration remain poorly understood. This limited pathophysiological understanding has hindered the development of diagnostic and prognostic biomarkers and has prevented the advancement of treatments for the sequelae of mild traumatic brain injury. We aimed to characterize the early electrophysiological and neurovascular alterations following repetitive mild traumatic brain injury and sought to identify new targets for the diagnosis and treatment of individuals at risk of severe post-impact complications. We combined behavioural, electrophysiological, molecular, and neuroimaging techniques in a rodent model of repetitive mild traumatic brain injury. In humans, we used dynamic contrast-enhanced MRI to quantify blood-brain barrier dysfunction after exposure to sport-related concussive mild traumatic brain injury. Rats could clearly be classified based on their susceptibility to neurological complications, including life-threatening outcomes, following repetitive injury. Susceptible animals showed greater neurological complications and had higher levels of blood-brain barrier dysfunction, transforming growth factor ß (TGFß) signalling, and neuroinflammation compared to resilient animals. Cortical spreading depolarizations were the most common electrophysiological events immediately following mild traumatic brain injury and were associated with longer recovery from impact. Triggering cortical spreading depolarizations in mild traumatic brain injured rats (but not in controls) induced blood-brain barrier dysfunction. Treatment with a selective TGFß receptor inhibitor prevented blood-brain barrier opening and reduced injury complications. Consistent with the rodent model, blood-brain barrier dysfunction was found in a subset of human athletes following concussive mild traumatic brain injury. We provide evidence that cortical spreading depolarization, blood-brain barrier dysfunction, and pro-inflammatory TGFß signalling are associated with severe, potentially life-threatening outcomes following repetitive mild traumatic brain injury. Diagnostic-coupled targeting of TGFß signalling may be a novel strategy in treating mild traumatic brain injury.

Head trauma analysis of laboratory reconstructed headers using 1966 Slazenger Challenge and 2018 Telstar 18 soccer balls.

Retired soccer players are presenting with early onset neurodegenerative diseases, potentially from heading the ball. It has been proposed that the older composition of soccer balls places higher strains on brain tissues. The purpose of this research was to compare the dynamic head response and brain tissue strain of laboratory reconstructed headers using replicas of the 1966 Slazenger Challenge and 2018 Telstar 18 World Cup soccer balls. Head-to-ball impacts were physically conducted in the laboratory by impacting a Hybrid III head form at three locations and four velocities using dry and wet soccer ball conditions, and computational simulation was used to measure the resulting brain tissue strain. This research showed that few significant differences were found in head dynamic response and maximum principal strain between the dry 1966 and 2018 balls during reconstructed soccer headers. Headers using the wet 1966 soccer ball resulted in higher head form responses at low-velocity headers and lower head responses as velocities increased. This study demonstrates that under dry conditions, soccer ball construction does not have a significant effect on head and brain response during headers reconstructed in the laboratory. Although ball construction didn't show a notable effect, this study revealed that heading the ball, comparable to goalkeeper kicks and punts at 22 m/s, led to maximum principal strains exceeding the 50% likelihood of injury risk threshold. This has implications for the potential risks associated with repetitive heading in soccer for current athletes.