Blood-brain barrier damage occurs even with mild head trauma

September 25, 2019

Science Daily/American Associates, Ben-Gurion University of the Negev

In a new study of adolescent and adult athletes, researchers at Ben-Gurion University of the Negev, Stanford University and Trinity College in Dublin have found evidence of damage to the brain's protective barrier, without a reported concussion.

For the first time, the researchers were able to detect damage to the blood-brain barrier (BBB), which protects the brain from pathogens and toxins, caused by mild traumatic brain injury (mTBI). The results were published this month in the Journal of Neurotrauma.

The researchers studied high-risk populations, specifically professional mixed martial arts (MMA) fighters and adolescent rugby players, to investigate whether the integrity of the blood-brain barrier (BBB) is altered and to develop a technique to better diagnose mild brain trauma.

"While the diagnosis of moderate and severe TBI is visible through magnetic resonance imaging [MRI] and computer-aided tomography scanning [CT], it is far more challenging to diagnose and treat mild traumatic brain injury, especially a concussion which doesn't show up on a normal CT," explains Prof. Alon Friedman, M.D., Ph.D. Dr. Friedman is a groundbreaking neuroscientist and surgeon, who established the Inter-Faculty Brain Sciences School at BGU.

The study shows that mild impact in professional MMA and adolescent rugby can still lead to a leaky BBB. If in a larger study the results are similar, the brain imaging techniques being developed could be used to monitor athletes to better determine safer guidelines for "return to play."

In this study, MMA fighters were examined pre-fight for a baseline and again within 120 hours following competitive fight. The rugby players were examined pre-season and again post-season or post-match in a subset of cases. Both groups were evaluated using advanced MRI protocol developed at BGU, analysis of BBB biomarkers in the blood and a mouthguard developed at Stanford with sensors that track speed, acceleration and force at nearly 10,000 measurements per second.

Ten out of 19 adolescent rugby players showed signs of a leaky blood-brain barrier by the end of the season. Eight rugby players were scanned post-match and two had barrier disruptions. The injuries detected were lower than the current threshold for mild head trauma. The researchers were also able to correlate the level of blood-brain barrier damage seen on an MRI with measurements from the mouthguard sensors.

"The current theory today is that it is the outer surface of the brain that is damaged in a concussion since, during an impact, the brain ricochets off of skull surfaces like Jell-O," Dr. Friedman says. "However, we can see now that the trauma's effects are evident much deeper in the brain and that the current model of concussion is too simplistic."

In the next phase of research, the group plans to conduct a similar study in a larger cohort to determine whether BBB disruptions heal on their own and how long that takes.

"It is likely that kids are experiencing these injuries during the season but aren't aware of them or are asymptomatic," Dr. Friedman says. "We hope our research using MRI and other biomarkers can help better detect a significant brain injury that may occur after what seems to be a 'mild TBI' among amateur and professional athletes."

https://www.sciencedaily.com/releases/2019/09/190925133626.htm

Repetitive impacts key to understanding sports-associated concussions

September 9, 2019

Science Daily/Trinity College Dublin

Scientists at Trinity College Dublin have announced a significant advance in our understanding of mild head trauma (concussive brain injury) and how it may be managed and treated in the future. It seems that repetitive impacts -- as opposed to single events -- cause the all-important damage to blood vessels in the brain.

Mild head trauma has come to the fore in recent years as being associated with collision and combat sports. However, it is also a very common injury in children and young adults and represents a significant challenge to physicians due to the lack of any robust biomarkers or objective imaging approaches to manage the injury.

"This was a hypothesis-driven project whereby we challenged the hypothesis that repetitive head trauma would induce damage to small blood vessels in the brain that we would then be able to image with a novel form of MRI-based brain scans," said Dr Matthew Campbell, Assistant Professor at Trinity.

The study, which was undertaken by the Trinity-led Concussion Research Interest Group (CRIG) used both sensor-enabled mouthguard technology developed by the group of Professor David Camarillo at Stanford University and dynamic contrast-enhanced MRI to confirm the number and severity of head impacts that would lead to the appearance of "leaky" blood vessels within the brain.

Participants of combat and collision sports such as mixed martial arts (MMA) and rugby took part in the clinical research study, which took four years to complete and is part of a wider longitudinal study, which is still ongoing.

Concussive brain injuries

While it is clear that concussive brain injuries cause clinical symptoms such as dizziness, nausea and confusion, these symptoms all occur independent of any adverse findings on CT or MRI scans, and/or without the presence of any clear blood-based biomarkers. Therefore, the clinical management of concussive brain injuries is challenging and needs new technologies to assist in diagnosis and rehabilitation.

Dr Colin Doherty, Consultant Neurologist at St James's Hospital and clinical lead on the study, added: "Our findings, for the first time, suggest that repetitive head trauma can lead to an MRI signal that we can definitively link to the number and severity of impacts to the head. It appears that the repetitive nature of these impacts as opposed to single events are causing damage to the capillaries of the brain."

The study reports that repetitive impacts to the head, not necessarily just concussions, are likely able to induce changes to the micro-vessels of the brain. It is these changes that are then readily visible when using a novel form of MRI-based imaging.

While the study was based on a selected group of MMA fighters and rugby players, the findings could eventually pave the way for more robust and objective return-to-play guidelines and improved player safety in the longer term.

"This study has highlighted the critical importance of continued efforts to study the underlying effects of concussive brain injuries in all sports. It is imperative that the governing bodies take note of these findings and work together to protect athletes now and in the future," added co-author Professor Mick Molloy, former Chief Medical Officer of World Rugby.

https://www.sciencedaily.com/releases/2019/09/190909130227.htm