CONFERENCE AGENDA

Day One - May 2, 2024

Registration & Continental Breakfast

Chairperson's Opening Remarks

Andreas Jeromin, Ph.D., Chief Scientific Officer, ALZ Path

Preclinical Research Trends Track - Track Chair's Opening Remarks

Reversing Post-traumatic Amnesia After Repeated Head-impact

Exposure to a high frequency of head impacts (HFHI) results in retrograde amnesia in mice. We used c-fos/TRAP2 ("engram") transgenic mice to study how HFHI alters the physiology of dentate gyrus neurons involved in learning a new memory. After fear conditioning we exposed mice to either sham or HFHI protocols. We found that when mice were presented with natural cues to recall the memory, the engram neurons in sham mice were activated, demonstrated synaptic plasticity, and sham mice recalled the memory. In contrast, the engram neurons in HFHI mice had reduced activity, were unable to undergo synaptic plasticity, and the HFHI mice displayed amnesia. To demonstrate that HFHI-induced amnesia is due to a synaptic deficit, we optogenetically stimulated the engram neurons and showed that the lost memory could be recalled in the HFHI brain. These data show that HFHI-induced amnesia is a physiological process instead of a pathological condition, and therapies targeting synaptic plasticity have potential for the reversal of chronic learning and memory deficits after repeated head impact.

Mark Burns, Ph.D., Professor, Vice-Chair, Department of Neuroscience, Georgetown University

Understanding the Neuroimmunology of Aging and Traumatic Brain Injury

Heterogeneity of pathoanatomical subtypes and diversity in the extent of injury contribute to differences in the pathogenesis of TBI. Although this heterogeneity can be influenced by many variables including sex and genetic variability; age and aging related processes remain key factors that determine the clinical outcomes after TBI. Alongside age, there is a growing consensus that neuroinflammation plays a key role in determining the pathophysiology of TBI. Given neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the neuro-immune responses that follow TBI. Dr. Main will present data displaying the temporal progression of secondary injury cascades including blood brain barrier dysfunction, and the secretion of pro-inflammatory cytokines and chemokines by resident microglial and astrocyte populations after injury. In addition, he will show how meningeal lymphatics link the brain and periphery and play an important bi-directional inflammatory role, with particular involvement in the drainage of immune cells after TBI. Finally, he will evidence how these combined responses are exacerbated with age, and discuss the implications of these findings in the broader context of secondary injury in TBI, and TBI-induced neurodegenerative disease.

Bevan Main, Ph.D., Assistant Professor, Georgetown University

Human Tau Isoform Expression Alters Acute and Chronic Progression of Traumatic Brain Injury

Brain injury is compared in knock-in mice (MAPTKI) that express all 6 human tau isoforms using the mouse tau promotor with wild-type mice that express 3 mouse tau isoforms. At 14 days post-injury, wild-type mice have axonal injury, demyelination and cognitive deficits. Many cognitive deficits in injured wild-type mice resolve by 90 DPI. In contrast, at 14 days post-injury, MAPTKI mice have less white matter injury and lack the cognitive deficits in wild-type mice. At 90 DPI, MAPTKI mice develop cognitive and memory deficits not present in wild type. Thus, expression of human tau greatly changes disease course in MAPTKI mice after a single closed head injury.

Peter Bergold, Ph.D., Professor of Physiology and Pharmacology, SUNY-Downstate Medical Center

White Matter Pathology in TBI: Clues to Therapeutic Opportunities for Intervention

Traumatic brain injury can produce white matter pathology that involves axon damage and demyelination, as well as neuroinflammation and vascular injury. Long axons in white matter tracts are especially vulnerable to damage from TBI. Axon signal conduction is highly sensitive to disruption of axon-myelin interactions. Myelination also provides trophic and metabolic support for axon function and survival. This talk will use neuroimaging, structural and molecular data to demonstrate a range of axon and myelin pathological features in white matter injury across times post-injury. Importantly, this data broadens the population of axons involved and reveals additional opportunities for therapeutic intervention to protect axons and promote recovery of function after traumatic axonal injury.

Regina Armstrong, Ph.D., Professor & Chair, Department of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services University

Track Follow Up Discussion & Question/Answer Session

Refreshment Break/Exhibit Viewing/Poster Session

Prevention, Prognostication, and Problems in Managing Pediatric Mild Traumatic Brain Injury - Track Chair's Opening Remarks

Rebekah Mannix, MD, MPH, Professor of Pediatrics & Emergency Medicine, Harvard Medical School

Prevention is the Best Medicine for Youth Concussion

This presentation will discuss fundamentals in concussion prevention with an emphasis on the following topics:

  • Can equipment prevent concussions?

  • Is there a biomechanical threshold for injury?

  • Are head impact sensors a useful tool to understand exposure?

  • What are other characteristics of a prevention-focused view of concussions?

Kristy Arbogast, Ph.D., Scientific Director, Minds Matter Concussion Program Research Director, Children's Hospital of Philadelphia

Biopsychosocial Influences on Concussion Recovery in Children and Adolescents

Recovery from pediatric concussion reflects a complex interplay of neurological, psychological, and environmental factors. This presentation will summarize recent findings from a large prospective cohort study of concussion in 8-17 year old children, linking recovery trajectories to neuroimaging, psychological resilience, and the parent and family environment. The findings suggest that concussion recovery involves multi-level influences of both injury and non-injury factors.

Keith Yeates, Ph.D., Professor, Department of Psychology, Ronald & Irene Ward Chair in Pediatric Brain Injury, University of Calgary

Prognostication in Pediatric Mild Traumatic Brain Injury

Predicting outcomes in mild traumatic brain injury is challenging given heterogeneities in injury biomechanics, individual host factors, and the current reliance on subjective self-report measures (i.e. gold standard). Prognostication in children is further complicated by the developing brain, which rapidly changes at different rates throughout middle childhood and adolescence. The presentation will describe recent attempts to understand how prognostication is affected by psychometric properties of self- and parental report, and how imaging and blood-based biomarkers may improve diagnosis and prognostication. Finally, we will discuss how large animal models can be used in parallel with clinical studies to shed light on injury biomechanics and mechanisms of injury.

Andrew Mayer, Ph.D., Professor of Translational Neuroscience, The Mind Research Network, University of New Mexico

Track Follow Up Discussion & Question/Answer Session

Making Sense of Conflicting Narratives About Traumatic Brain Injury Outcomes

As the scientific literature on TBI grows, so does the diversity of research findings that appear to reach conflicting conclusions about the natural history of clinical recovery. For example, studies of “mild” TBI have reported both that recovery is almost always rapid and complete and that there is a high prevalence of long-term consequences of injury. Dr. Nelson will summarize findings from recent large, prospective studies of TBI on the early and long-term consequences of injury, including what we now know about the factors that explain variable patient outcomes and priority areas for future research.

Lindsay Nelson, Ph.D., ABPP, Associate Professor and Director of Translational Research, Department of Neurosurgery, Medical College of Wisconsin

Luncheon

Biomarker Research Track -Track Chair's Opening Remarks

Cheryl Wellington, Ph.D., Professor, Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Mind Research Network, University of British Columbia

You Injure the Body You Have: Implication of Body Habitus on Inflammatory Response and Recovery from Mild Traumatic Brain Injury

Obesity is a disease state which is associated with chronic circulatory inflammation and numerous baseline comorbidities. These conditions have the potential to increase short- and long-term inflammatory responses to physical trauma in comparison to a normal mass patient. Higher acute inflammatory markers predict worse outcomes from mild traumatic brain injury (mTBI). To date, little is known about the role of baseline (at time of injury) obesity and outcomes from mTBI. The purpose of this presentation is to describe differences in inflammatory response to mTBI between obese and non-obese patients and the association between inflammatory response, comorbid health conditions, and long-term outcomes following the injury.

Shawn Eagle, Ph.D., Research Assistant Professor, Department of Neurological Surgery, University of Pittsburgh

The Utility of Acute Neurotrauma Biomarkers

Ava Puccio, RN, Ph.D., Associate Professor of Neurological Surgery, Co-Director Neurotrauma Clinical Trials Center, University of Pittsburgh

Blood-Based Biomarkers of Epileptogenesis after Traumatic Brain Injury; Clinical Studies

Post-traumatic epilepsy (PTE) is one of the major complications following severe traumatic brain injury. The epileptogenic process leading to PTE is currently poorly understood but likely multifactorial and crosses multiple modalities. Without a full understanding of the underlying pathobiological process, there will be no cures for PTE. Identifying blood borne protein biomarkers of the TBI-induced epileptogenic process provide not only diagnostic and prognostic information but also help to identify potential molecular targets for developing therapeutic interventions. Dr. Agoston will present blood-based biomarker data identified in the clinical studies from the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx). EpiBioS4Rx is an NINDS-funded international, multicenter Center without Walls (CWOW) research program with the objectives of developing the techniques to identify biomarkers to determine patient populations at risk and likely to benefit from PTE prevention therapies, rendering such future clinical trials cost-effective. He will discuss the power of using Machine Learning in analyzing and interpreting blood borne protein biomarker data to identify pathobiologies underlying the development of PTE, high-risk individuals, and identifying disease modifying therapies.

Denes Agoston, MD, Ph.D., Professor, Department of Anatomy, Physiology & Genetics , Uniformed Services University

Track Follow Up Discussion & Question/Answer Session

Advances in Sport/Concussion Research - Track Chair's Opening Remarks

SHRed Concussions: Primary Prevention of Youth Sport-related Concussions

This presentation will include evidence informing best practice and policy in the prevention of concussions in youth sport across rule changes, personal protective equipment, and training strategies.

Carolyn Emery, Ph.D., Professor, Faculty of Kinesiology, University of Calgary

Refreshment Break/Exhibit Viewing/Poster Session

Key findings from the CARE (Concussion Assessment, Research and Education) Consortium

This presentation will provide key evidence from the CARE Consortium, including relevant data on the intermediate and long term effects of concussion in college varsity athletes and military service academy members.

Steven Broglio, Ph.D., Professor of Kinesiology, Neurology and Physical Medicine & Rehabilitation, Director, U-M Concussion Center, Director, NeuroTrauma Research Laboratory, University of Michigan

Neurologic Function Across the Lifespan: A Prospective, Longitudinal, and Translational Study of Former NFL Players

(NFL-LONG) has assessed a cohort of former National Football League players, some for as long as 20 years. In this update, Dr. Meehan will discuss their current health-related quality of life, how it compares to age matched men in the general population, and describe associations between the concussions they sustained and their current health related quality of life measures. He will discuss murine models of repeated concussions and the potential for future therapies. He will also briefly discuss the future plans of the study.

William Meehan III, Ph.D., Director, Mitchell Center for Sports Injury Prevention, Division of Sports Medicine, Boston Children's Hospital

Rehabilitation Following Concussion: Optimizing Evidence Informed Care and Considerations for Multisystem involvement

This presentation will summarize the latest evidence for rehabilitation following concussion – including both global and targeted rehabilitation following concussion across pediatrics and adults.

Kathryn Schneider, Ph.D., PT, Associate Professor, Clinician Scientist, University of Calgary

Track Follow Up Discussion & Question/Answer Session

Funding Opportunities for Traumatic Brain Injury Research and Therapy Development at the National Institute of Neurological Disorders and Stroke (NINDS/NIH)

This session will provide an opportunity to learn about various funding mechanisms, programs and current funding opportunities related to TBI research and therapy development at the National Institute of Neurological Disorders & Stroke (NINDS/NIH). Attendees will have an opportunity to connect with Program Directors from two divisions at NINDS: Dr. Hibah Awwad - Division of Neuroscience and Dr. Rebecca Roof - Division of Translational Research. Topics covered will be inclusive for scientists of all career stages. Attendees will be able to ask questions and to share tips for preparing grant applications.

Hibah O. Awwad, Ph.D., Program Director, Traumatic Brain Injury, Division of Neuroscience, NINDS, National Institutes of Health
Becky Roof, Ph.D., Program Director, IGNITE, Project Manager, BPN, Division of Tranlational Research, NINDS, National Institutes of Health

Evening Reception

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