Drs. Shaun Carlson and Yijen Wu, University of Pittsburgh

At the neuron level, mild traumatic brain injury (mTBI) may create changes (bioenergetic) undetected by current assessments. Repeated MRIs following mTBI will:

• Identify specific brain regions exhibiting impaired bioenergetics;

• Track bioenergetic changes;

• Assess the impact on neurobehavioral dysfunction.

Findings will support grant proposals for future research through NIH and others.

Dr. Pulkit Grover, Carnegie Mellon University and Boyle Cheng, Allegheny Health Network

Impairments of executive functions are common after brain injuries. Neurostimulation has possibilities, but sites are often inaccessible to current non-invasive stimulation technologies. Researchers at Carnegie Mellon University and Allegheny General Hospital intend to develop a non-invasive/minimally invasive way, named DeepVibe, to deliver this treatment and make it accessible to more TBI patients.

They outline a three-phase project:

1. Data-driven modeling

2. Cadaver studies

3. Human studies

Dr. Patrick Kochanek, University of Pittsburgh and Dr. Ruchira Jha, Barrow Neurological Institute

Using mice, researchers will quantify the cerebellar damage after mild TBI and define the microglial response to injury. Then microglial subtypes will be defined using single-cell RNAseq of the cerebellum. These clusters will facilitate future drug development.

Dr. Julia Kofler, University of Pittsburgh

Dr. Kofler and her team at the National Sports Brain Bank plan to compare four digital cognitive testing platforms that can be administered remotely and examiner-independent, which would enable repetitive testing of large number of participants.

This project has three aims:

1. To compare each digital platform to paper-and-pencil tests in different cognitive domains.

2. Assess accuracy of each platform in predicting diagnostic category compared to consensus diagnosis by clinician experts.

3. Collect feedback from participants re: each platform to predict likelihood of adherence to longitudinal repetitive testing.

Learn more about the University of Pittsburgh National Sports Brain Bank.

Dr. Nitin Agarwal, Barnes Jewish Hospital at Washington University in St. Louis

Traumatic brain injury (TBI) is multifaceted and complex. Dr. Agarwal and his team are utilizing Diffusion Basis Spectrum Imaging (DBSI) to analyze axonal injury and inflammation in Traumatic Brain Injury (TBI) patients, comparing their MRI scans with healthy controls to identify specific microstructural changes. This approach seeks to overcome the limitations of current imaging techniques by providing a more sensitive and specific assessment of nerve injury and inflammation. Furthermore, it aims to correlate these DBSI-derived metrics with neurological impairments, employing machine learning and deep neural network analyses to predict TBI severity, progression, and clinical outcomes, potentially establishing DBSI as a novel, noninvasive biomarker for TBI.

Dr. Patrick Kochanek, University of Pittsburgh and Dr. Ruchira Jha, Barrow Neurological Institute

This study investigates the mechanisms and potential preventive treatments for diffuse brain swelling and long-term cognitive impairments resulting from sports-related concussions and repeated mild head injuries.

Despite the rarity of severe swelling with high mortality rates, mild injuries are common and can lead to significant neurological issues through mechanisms like energy failure, neuroinflammation, and apoptosis.

With initial funding from the Chuck Noll Foundation, Drs. Kochanek and Jha, are employing single-cell RNA sequencing to explore the cellular and molecular pathways involved in these injury responses. The goal is to pave the way for precision medicine approaches by identifying specific cell types, genes, and pathways that contribute to brain swelling and cognitive deterioration.

Researchers aims to provide crucial preliminary data for further studies, potentially influencing treatment strategies for affected athletes by advancing understanding at the single-cell level.

Learn more about Dr. Jha and Dr. Kochanek and their work.

Drs. Shawn Eagle and David Okonkwo, University of Pittsburgh Medical Center

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. Their goal is to improve understanding of concussion susceptibility in relation to obesity and guide health decisions.

Dr. Eagle and his UPMC team believe their research will improve on prior work and modernize the field of brain trauma in several ways, such as:

• 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

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.

Read about how Dr. Kraft has teamed up with a grad student at Western Carolina University’s Engineering Technology program to complete this project.

Drs. Anthony Kontos, Christina Master, Mickey Collins, Kristy Arbogast, and Sarka Southern, UPMC Sports Medicine and The Children’s Hospital of Philadelphia

The project objective was 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. Daryl Fields, Justin Davanzo, and David 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.

Dr. Boyle Cheng, 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, Dr. Cheng and his team at AHN are conducting this 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).

Read in more detail about this trial here.

Dr. Rudy Casetellani, West Virginia University, Rockefeller Neuroscience Institute

This study aimed to investigate the potential causal links between traumatic brain injury (TBI) or exposure to contact sports and neurodegenerative diseases, focusing on tauopathy in brain tissue and examining amateur athletes for changes attributed to repetitive head trauma. Dr. Castellani seeks to determine if chronic traumatic encephalopathy (CTE) neuropathology falls within normal population variability without contributing to neurological or psychiatric symptoms, is insignificant among a random sample of amateur athletes, and is negligible in female athletes.

Drs. Julia Kofler and Oscar Lopez, University of Pittsburgh

This project, funded in partnership with R.K. Mellon and The Pittsburgh Foundation, established a brain bank focused on a non-selective cohort of contact sport participants.

In collaboration with the Pittsburgh Steelers, both retired professional players are welcome to participate in this donation program, as well as amateur athletes with or without any prior history of concussion.

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.

In May 2023, former Steelers Jerome Bettis and Merril Hogue both pledged their brains to the project and encouraged their fellow athletes to support the effort and help make sports safer for the next generation.

To learn more about the NSBB go to their website here.

Drs. Ruchira Jha and Patrick Kochanek, University of Pittsburgh

This research focused on a unique channel (Sur1-Trpm4) that has emerged 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.

Learn more about Dr. Jha and Dr. Kochanek and their work.

Dr. Shaun Carlson, University of Pittsburgh

Dr. Carlson investigated the effect of levetiracetam (commonly known as 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. Findings suggest that a higher dose of levetiracetam may be needed to improve motor and spatial learning after repeated mild traumatic brain injuries. The effects of levetiracetam treatment on synaptic protein abundance and intrasynaptic vesicular pools will be assessed in future research.

Dr. Joshua 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 modality types for both improved recovery from concussion and neuroprotective ability against future concussions.

Drs. Amelia Versace and Anthony 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 collected 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 had a clinical follow-up assessment at 3-week, 3-month, 6-month and 1 year to determine changes in cognitive and psychiatric symptoms following concussion.

Learn more about Dr. Versace and her team’s research here.

Drs. Anthony Kontos and Mickey Collins, UPMC Sports Medicine

Using a randomized controlled trial (RCT) design, researchers analyzed 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, vestibular-ocular) and cognitive impairment in adolescent patients with vestibular clinical profiles following sport-related concussion (SRC).

Learn more about their findings here.

Drs. C. Edward Dixon and Shaun Carlson, University of Pittsburgh

Researchers seek 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. Their study examined 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.

Dr. Frank 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, researchers sought to 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.

Dr. Pulkit Grover, Carnegie Mellon University

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 sought to advance a technique that predicts which brain injuries are likely to worsen before that 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.

Learn more about Dr. Grover and his team’s project.

Drs. Ava Puccio, Jessica Gill, and Michael McCrea, University of Pittsburgh and Medical College of Wisconsin

Researchers in this study are 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).