Dr. Reuben Kraft: The Pennsylvania State University

This study addresses the measurement of “on the field” impacts, the extent that impact has on the dynamic intracranial brain tissue and using that data to measure and predict brain injury. Sensors are now being placed in mouth guards to measure impact. The proposed research will assess the correlation of the data on the impacts with athletes who subsequently have or do not have a concussion. This would aid in the diagnosis of mild traumatic brain injury that is difficult to diagnose. In addition, the functional area of the brain impacted could be determined to assist in developing the treatment plan for that individual.

Drs. Shawn Eagle and David Okonkwo: UPMC

Researchers will “examine the impact of obesity on trajectories of blood- based biomarkers of brain injury and on profiles of traumatic brain injury recovery across specific (subtypes) of obesity … . The goal is to improve understanding of concussion susceptibility in relation to obesity and guide health decisions.”

The researchers feel that their research design will “improve on prior work and modernize the field of brain trauma in several ways.”

• Leverage the ready availability of smartphones in the United States

• Modify surveys to improve researchers’ ability to build valid statistical models

• Utilize machine learning techniques to identify obesity endotypes

• Expand upon the definition of obesity in the traumatic brain injury literature

• Enroll 50% females to be able to investigate potential differences by sex

Drs. Patrick Kochanek and Ruchira Jha: University of Pittsburgh and Barrow Neurological Institute

“Diffuse brain swelling after sports-concussive injuries, although rare, is associated with a high mortality rate. Conversely, repeated mild-head injuries without (or with minimal) swelling, are common and can impair long-term cognition via multiple secondary injury cascades (e.g., energy failure, neuroinflammation, apoptosis). In both these situations, little is known about underlying mechanisms; no preventive treatments are available. Given the profound and lifelong implications of these secondary-injury processes in young athletes, there is a critical unmet need to characterize, prevent and target both high-risk brain swelling and deleterious secondary injury processes that increase risk of neurological disability.

“Initial funding from the Chuck Noll Foundation has also allowed (these researchers) to begin applying … single-cell RNA sequencing to address this important problem.” Continued research at the single cell level is proposed and is intended to identify cell types, genes, and biological pathways relevant to understanding different injury models. “This work will initiate a paradigm shift towards precision medicine and deconstruct the heterogeneous individual response to athletic head injury at the single cell level leveraging a key pathway critical to secondary injury processes responsible for cerebral edema and cognitive outcome.”

“Results from this work are expected to generate important preliminary data for an NIH R01 grant proposal translating these findings to human patients.”

Dr. Nitin Agarwal: Barnes Jewish Hospital — Washington University in St. Louis

Traumatic brain injury (TBI) is multifaceted and complex. “The diversity of impaired molecular, cellular, and systemic processes challenges identification of optimal treatments and limits the ability to predict outcomes.” … “As a result, there is an urgent and unmet need to identify and develop biomarkers to aid in diagnosing, selecting optimal treatments, and predicting clinical outcomes.” This application proposes to start the “the development of a novel non-invasive imaging biomarker …with an innovative, non-invasive imaging approach called diffusion basis spectrum imaging (DBSI).”

“DBSI can detect the underlying subclinical tissue pathology, a feature that would be critical for predicting long-term outcomes across the heterogeneous population of TBI patients. As such, employing DBSI may have a high level of utility for professional football athletes to detect…TBI.”

Drs. Cheng, Snell, Giannoukakis, and Cheema: Allegheny Health Network

Some patients who experience moderate-to-severe traumatic brain injury (TBI) develop a systemic inflammatory response syndrome (SIRS) that fuels severe respiratory distress/acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. To prevent the development of SIRS, the researchers propose a pilot study to assess the use of non-invasive vagus neurostimulation (nVNS) as a drug-free “bioelectronics medicine” in patients who experience moderate-to-severe traumatic brain injury (TBI).

Drs. Fields, Davanzo, and Okonkwo: University of Pittsburgh

The investigators from UPMC and AHN propose to collect preliminary data on the prognostic use of spinal csf serotonin in understanding clinical outcomes in patients with spinal cord injuries. They theorize that patients with low CSF serotonin will exhibit limited functional recovery 6 months post injury.

Drs. Kontos, Master, Collins, Arbogast, and Southern: UPMC Sports Medicine & The Children’s Hospital of Philadelphia

The objective of the proposed project is to conduct a collaborative, multisite study of saliva biomarkers for domain-specific symptoms and impairment reflecting current concussion clinical subtypes among 200 pediatric patients within 7 days of a concussion.

Drs. Versace and Kontos: University of Pittsburgh

The purpose of the study is to examine the extent to which levels of saliva microRNAs in the early (i.e. acute, early subacute) phase of injury can predict the severity of short and long-term symptomatology.

The research team have been collecting saliva specimens in adolescents who - by virtue of having received a recent (<7±3 days) diagnosis of concussion - have been enrolled in an on-going NIMH-funded ROI study investigating Concussion in Adolescents at Risk for Emotional dysregulation (iCARE; ROI MH114881). After saliva (and MRI) data collection, concussed adolescents are clinically followed-up at 3-week, 3-month, 6-month and 1 year to assess changes in cognitive and psychiatric symptoms following concussion.

Dr. Hagen: West Virginia University, Rockefeller Neuroscience Institute

Traditionally, acute physical and cognitive rest is the primary route for recovery from concussion, while metrics such as symptom scores and cognitive tests are tracked to determine return to play for athletes, or return of duty for the military. This research project proposes to study recovery modalit types for both improved recovery from concussion and neuroprotective ability against future concussions.

Dr. Carlson: University of Pittsburgh

This project aims to assess the effect of levetiracetam (Keppra), an FDA approved anti-convulsant, on synaptic dysfunction following repetitive mild traumatic brain injuries. The effect of levetiracetam on synaptic protein abundance, the pre-synaptic vesicular pool, and neurotransmitter release will be determined.

Drs. Jha and Kochanek: University of Pittsburgh

This research focuses on a unique channel (Sur1-Trpm4) that is emerging as a key contributor to brain swelling and clinical outcome after many different types of injuries including traumatic brain injury (TBI) and stroke. It is unusual, in that the channel is not known to be present in the brain normally, which makes it an attractive target to block without an extensive side effect profile.

Drs. Kofler and Lopez: University of Pittsburgh Brain Bank for Contact Sports Participants

This proposal will establish a brain bank focused on a non-selective cohort of contact sport participants. In collaboration with the Pittsburgh Steelers, all retired players will be invited to participate in this donation program. Subjects who agree to participate, will be asked to complete a questionnaire assessing their medical history, clinical symptoms and trauma exposure. In a second future phase, the research will expand to include detailed neurocognitive evaluations at our center to obtain objective longitudinal data about cognitive performance.

This project will establish a rich clinical and pathological database that will allow us to examine the natural history of cognitive deficits in retired football players and their corresponding brain lesions at autopsy. The data obtained will provide the essential scientific knowledge to better understand the pathological mechanisms involved in the etiology of CTE in football players and other athletes.

Drs. Puccio, Gill, McCrea, and Okonkwo: University of Pittsburgh and Medical College of Wisconsin

This study is examining biomarkers in both peripheral blood and novel sweat patch technology for proteins that potentially build up and may cause neurodegeneration, such as chronic traumatic encephalopathy (CTE).

Drs. Grover, Behrmann, Tarr, Kelly, Elmer, and Shutter: Carnegie Mellon University and University of Pittsburgh

When a head-trauma arrives in the emergency room, the most difficult question a brain injury clinician faces is: is the patient going to recover, or is their condition going to worsen over time because of secondary brain damage? While several behavioral tests attempt to estimate how much damage has already been done, this project seeks to advance a technique that predicts which brain injuries are likely to worsen before the worsening happens, thus providing clinicians valuable information to change the course of treatment. We do so by advancing on two fronts: (i) Novel noninvasive detection algorithms for “brain tsunamis,” which are waves of neural silencing that slowly develop on the surface of the injured brain, causing further injuries; (ii) New technology, that we call goEEG, that is able to measure high resolution neural signals noninvasively for all individuals, including those with coarse and curly hair common in individuals of African descent.

Dr. Yeh: University of Pittsburgh

Diffusion MRI fiber tracking has arisen as the only non-invasive way to map brain connections and assess their structural integrity. Using the most up-to-date fast imaging sequences, we can acquire high quality data of patients on standard clinical scanners. This advancement has gained considerable interest because of its roles in mapping brain connections for sport related brain injury.

The team applied high accuracy fiber tracking to study the chronic brain injury in retired NFL players and revealed their damaged pathways. This allowed them to better understand the cause of their symptoms and plan for further rehabilitation.

Drs. Dixon, Carlson: University of Pittsburgh

This project seeks to determine if one of the brain’s fatty acids can improve the functioning of neurons in the brain that have been damaged by multiple traumatic brain injuries. This study will examine the effects of Docosahexaenoic Acid (DHA) treatment on tests of balance and cognition and specific aspects of the neurotransmission deficits that occur after experimental repetitive mild traumatic brain injury (RMTBI) in rats.

Drs. Kontos and Collins: UPMC Sports Medicine

The purpose of the study is to determine, using a randomized controlled trial,(RCT) design the effectiveness of a precision, vestibular treatment compared to standard of care (i.e., behavioral management interventions) for reducing recovery time, symptoms, and vestibular (i.e., balance, vestibulo-ocular) and cognitive impairment in adolescent patients with vestibular clinical profiles following sport-related concussion (SRC).