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October 4, 2021

Central Standard Time (CST)

9:30 am Chairperson’s Opening Remarks

Andreas Jeromin, Ph.D., Chief Scientific Officer, Cohen Veterans Bioscience

9:40 am Salivary Small Non-coding RNAs as Biomarkers of Sport Concussion: Key Messages of the SCRUM study, Applications and Limitations
Small non-coding RNAs (sncRNAs) are particularly abundant in saliva and after brain injury, their concentrations change very rapidly, thus offering the potential for an ideal non-invasive test. Much remains to be understood about their biological pathways and functions. The talk will cover the discovery, clinical validation and potential applications of salivary sncRNAs in the field of sport concussion.
Antonio Belli, MD, Professor of Trauma Neurosurgery, Director of the NIHR Surgical Reconstruction and Microbiology Research Centre (Trauma Research), University of Birmingham

10:15 am Traumatic Encephalopathy Syndrome (TES): Chasing a Moving Target
In this presentation, Dr. Dams-O'Connor will discuss research applications of the 2021 consensus-based research criteria for TES, the proposed clinical correlate of chronic traumatic encephalopathy (CTE). Ongoing efforts to permit in-vivo clinical diagnosis of post-traumatic neurodegenerative pathologies will require refinement of validated clinical diagnostic criteria that are both sensitive and specific. Diagnostic criteria for TES were informed by retrospective postmortem characterizations of individuals who were diagnosed with CTE, and CTE diagnostic criteria have since been refined. Having been developed in cohorts consisting primarily of male American football players, the relevance of current TES criteria to individuals with distinct head trauma exposure histories, including isolated TBI, is unclear. We applied the 2021 TES criteria to prospectively collected psychometric data from the ongoing Late Effects of TBI (LETBI) study, and we will present the rates of TES symptomatology across domains and injury exposure profiles. The implications of these findings for in-vivo clinical diagnosis of post-traumatic neurodegenerative pathologies will be discussed.
Kristen Dams O'Connor, Ph.D., Director, Brain Injury Research Center, Professor, Icahn School of Medicine at Mount Sinai

10:50 am Morning Break - Visit with Sponsors/Poster Viewing/Networking

11:15 am Evaluation of CSF and Blood Biomarkers in Spinal Cord Injury

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

11:50 am Novel Blood and Sweat Biomarkers that Relate to Brain Injuries
Jessica Gill, Ph.D., RN, FAAN, Acting Deputy Director, Division of Intramural Research, Lasker Clinical Research Scholar, Sr. Investigator, National Institute of Nursing Research (NINR), National Institutes of Health

12:25 pm Lunch Break - Visit with Sponsors/Poster Viewing/Networking

1:10 pm Establishing Ground Truth in TBI Research: If Replication is the Answer, What Are the Questions?
While the current replication crisis has encouraged a period of scientific introspection, one critical next-step for determining which hypotheses are established and which need further support remains unclear. We used bibliographic referencing and a network science approach to understand how the brain injury literature has evolved over the last 70 years (>50,000 articles) including how distinct research communities within TBI have emerged over time and how critical findings have operated as drivers of our science. The goal is to identify "ground truths" that operate as the anchors in the TBI literature as well as hypotheses that require additional support and can be targets for replication.
Frank Hillary, Ph.D., Professor of Psychology & Neurology, Penn State University 

1:45 pm A Novel Route to Neuroprotection in Chronic Traumatic Brain Injury (TBI Young Investigator Virtual Summer Conference Co-Winner)
Chronic neurodegeneration in survivors of traumatic brain injury (TBI) is a major cause of morbidity, and at present there are no medicines that mitigate this progressive and debilitating form of nerve cell death. We have found that P7C3-A20-mediated pharmacologic restoration of the blood–brain barrier (BBB) in mice 12 months after TBI is associated with complete cessation of chronic axonal neurodegeneration and full cognitive recovery. Moreover, the beneficial therapeutic effects persisted for months after treatment cessation. Electron microscopy revealed the P7C3-A20 treatment achieved full repair of TBI-induced breaks in cortical and hippocampal BBB endothelium, and immunohistochemical staining identified restoration of normal BBB endothelium length, increased brain capillary pericyte density, increased expression of BBB tight junction proteins, reduced brain infiltration of immunoglobulin, and attenuated neuroinflammation. Collectively, our results show that chronic neurodegeneration and cognitive impairment can be reversed at distal time points after TBI, and identify pharmacologic restoration of the BBB as a putative treatment strategy for chronic TBI patients.
Edwin Vazquez-Rosa, Ph.D., RN, Senior Research Associate, Case Western Reserve University

2:10 pm Neuroprotective Effects of Tamoxifen in Xenopus Laevis Model of Focal Impact Injury
Estrogen compounds and selective estrogen receptor modulators have been shown to produce neuroprotective effects in mammalian models of TBI and spinal cord injury. After extensive work validating the Xenopus laevis tadpole as an effective model of focal impact injury, we show that the selective estrogen receptor modulator tamoxifen improves TBI-induced behavioral deficits, modulates neuronal cell death and astrocyte activation, and reduces post-injury edema. Moreover, our preliminary findings reveal sex differences in the response to injury in the Xenopus laevis TBI model.
Sydnee Spruiell Eldridge, M.A., Ph.D Candidate, Graduate Teaching Fellow, Cellular & Molecular Biology Department, University of Houston

2:35 pm PANEL SESSION: Toward a Universal Pipeline for Behavioral and MRI Data Harmonization in the Study of Traumatic Brain Injury
The goal of this session is to outline recent progress in data sharing and harmonization efforts in the study of TBI. The ENIGMA Brain Injury working group has an NIH-funded effort to create new pathways for data aggregation and harmonization. The goal is to create novel processing streams for international collaboration permitting conservative data combination and modeling of within and between-site affects on data fidelity. The outcome of this research will be to provide the TBI community with novel methods and freely available softwares that aid in data combination by also in determining when distinct data types can and cannot be combined in the service of studying TBI.
Frank Hillary, Ph.D., Professor of Psychology & Neurology, Penn State University
David Tate, Ph.D., Associate Professor, Co-Director, TBI and Concussion Center, University of Utah School of Medicine
Emily Dennis, Ph.D., Assistant Professor, Neurology, University of Utah School of Medicine

3:25 pm End of Day's Sessions

October 5, 2021

Central Standard Time (CST)

9:30 am Biomarkers in Neurotrauma: Results from TRACK-TBI and University of Pittsburgh Pilot Studies
Ava Puccio, RN, Ph.D., Assistant Professor, Co-Director, Neurotrauma Clinical Trials Center, University of Pittsburgh, School of Medicine, Neurological Surgery

10:05 am TRACK-TBI: A 10 Year Journey to Transform Research and Clinical Knowledge in TBI

Geoff T. Manley, MD, Ph.D., Professor & Vice Chairman of Neurological Surgery, Co-Director, Brain & Spinal Injury Center, University of California San Francisco

10:40 am Morning Break - Visit with Sponsors/Poster Viewing/Networking

11:05 am Phenotypes of TBI: Do They Exist and How Can We Use Them
Dr. Pugh will provide results from a systematic review of the literature on phenotypes of TBI, Identify how existing studies can be used to advance research and clinical care, identify gaps that exist in research, and propose a research agenda to advance research with the ultimate goal of improving precision medicine in TBI acute care and rehabilitation.
Mary Jo Pugh, Ph.D., RN, Professor, Department of Medicine, Division of Epidemiology, University of Utah School of Medicine

11:40 am Sex-Gender Differences in Brain Injury and Why it Matters
This presentation will provide a broad overview of sex and gender differences in brain injury. The presenter will address why these differences are important for patients, families and clinicians to consider in care plans for women and girls. She will also describe how a lack of medical understanding can inhibit diagnosis and appropriate intervention across the care continuum. Finally, she will articulate the factors that may account for sex and gender differences in TBI incidence, severity and recovery.
Katherine Snedaker, LCSW, Founder & Chief Executive Officer, PINK Concussions

12:15 pm Lunch Break - Visit with Sponsors/Poster Viewing/Networking

1:00 pm Reducing Acetylated-tau is Neuroprotective in Brain Injury (TBI Young Investigator Virtual Summer Conference Co-Winner)
Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer’s disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.
Min-Kyoo Shin, Ph.D., Senior Research Associate, Case Western Reserve University

1:25 pm A CRISPR Interference Screen in iPSC-derived Cerebral Organoids Identifies Novel Therapeutic Targets for Traumatic Brain Injury (TBI Young Investigator Virtual Summer Conference Co-Winner)
Traumatic brain injury (TBI) is a major environmental risk factor for neurodegenerative diseases such as frontotemporal dementia (FTD). To address a need for higher throughput and human-specific models, we generated cerebral organoids from induced pluripotent stem cells and inflicted injury using high-intensity focused ultrasound (HIFU). This model recapitulates progressive neurodegeneration, astrogliosis, tau and TDP-43 phospho-proteinopathies, as well as hallmark transcriptional programmes. These phenotypes are exacerbated in organoids derived from patients with FTD. A CRISPR interference screen identified mechanosensory channel (MSC) inhibition as a protective pathway against TBI in vitro. Indeed, concurrent treatment with small molecule inhibitors of MSCs showed a neuroprotective effect. These treatments reduced neuronal Ca2+ influx as well as tau and TDP-43 phosphorylation following injury. Single cell transcriptomics of glutamatergic neurons suggest that MSC inhibition attenuates the integrated stress response via EIF2 signaling. Collectively, MSC inhibition is a promising novel therapeutic option that may mitigate the course of disease.
Jesse Lai, Ph.D., Postdoctoral Fellow, University of Southern California

1:50 pm Blood-brain Barrier Dysfunction After TBI: A Target for Neuroprotective Therapies
Ramon Diaz-Arrastia, MD, Ph.D., Associate Director for Clinical Research, Center for Neurodegeneration and Repair, Director of TBI Clinical Research Center, Presidential Professor of Neurology, Penn Medicine

2:25 pm Where the Heck is ATE (Acute Traumatic Encephalopathy)?
If there is a CTE, doesn't there have to be an ATE? It is generally accepted that Chronic Traumatic Encephalopathy (CTE) is manifest by specific symptoms and anatomic changes. If a chronic condition is possible, then isn't there by definition, some kind of acute manifestation? This presentation proposes the diagnostic criteria for the definition of Acute Traumatic Encephalopathy.
W. Frank Peacock, MD, FACEP, Professor, Vice Chair for Research, Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine 

3:00 pm Head Injury and the 25-Year Risk of Dementia
In this presentation, Dr. Schneider will discuss TBI epidemiology and review several key prior studies on TBI and dementia risk and highlight literature gaps. She will then describe the Atherosclerosis Risk in Communities (ARIC) Study, including head injury and dementia definitions and statistical methods. Finally, she will present associations of TBI, TBI frequency, and TBI severity with 25-year risk of dementia.
Andrea Schneider, MD, Ph.D., Assistant Professor of Neurology, Penn Medicine

3:35 pm End of Day's Sessions

October 6, 2021

Central Standard Time (CST)

9:30 am Leveraging Brain Plasticity for Improvement in Attention and Working Memory in Mild Traumatic Brain Injury
Attention and working memory deficits underlie the most commonly reported cognitive complaints associated with mild traumatic brain injury. Neuromodulation, specifically through transcranial Direct Current Stimulation (tDCS), has shown promise in numerous areas including treatment resistant epilepsy, depression, impulsivity, and alcoholism. Dr. Hungerford will present preliminary findings from on ongoing randomized clinical trial of tDCS for Service Members with a history of mTBI and current cognitive complaints. Data will include EEG, rsMRI, Bethesda Eye and Attention Measure (BEAM) performance, and neuropsychological test scores.
Lars Hungerford, Ph.D., Senior Clinical Research Director, Traumatic Brain Injury Center of Excellence (TBICoE)

10:05 am Circuit-targeted Therapeutics for Traumatic Brain Injury
With recent advances in brain circuit mapping, we now have potential treatment targets for a wide range of neuropsychiatric disorders, many of which can arise as a consequence of TBI. In this talk, Dr. Siddiqi will discuss new research in identifying brain circuits that are causally implicated in different symptoms/disorders and describe how these circuits are being translated into new treatment targets for transcranial magnetic stimulation, deep brain stimulation, and other brain circuit-targeted therapies.
Shan Siddiqi, MD, Instructor in Psychiatry, Director of Psychiatric Neuromodulation Research, Harvard Medical School, Brigham & Women's Hospital

10:40 am Morning Break - Visit with Sponsors/Poster Viewing/Networking

11:05 am Preclinical and Clinical Characterization of PNT001, a Monoclonal Antibody That Recognizes cis-pT231 Tau
Pinteon Therapeutics has developed PNT001, a humanized full-length IgG4 monoclonal antibody targeting the cis conformation of pT231 tau with high affinity and selectivity. PNT001 selectively recognizes pathology in brain tissue from PSP, AD and CTE patients but not normal healthy volunteers. Murine versions of PNT001 improve biochemical and functional endpoints in the Tg4510 mouse model of tau over-expression and in a mouse model of TBI. PNT001 was safe and well tolerated in a Single Ascending Dose study in healthy volunteers. A 3 month, Multiple Ascending Dose study has initiated in TBI patients.
Kelly Foster, Ph.D., Senior Director, Biology, Pinteon Therapeutics

11:40 pm Will I catch you if you Fall? The ED perspective on Elderly Falls and TBI
In this presentation, Dr. Kuehl will discuss the challenges ED providers face in diagnosing and managing TBI in the elderly. He will highlight the immediate needs for acute diagnosis and prognosis in this population and will explore emerging and future diagnostics to improve outcomes for what is a major public health problem. He will also discuss his team's planned multi-centered elderly TBI study and his current work finding missed elderly TBI injuries. A significant portion of his talk will focus on how very wrong we are with national estimates of elderly TBI. Finally, he will describe a multimodal future approach with examples from the Carilion Brain Injury Center..
Damon Kuehl, MD, Chair, Brain Injury Center, Virginia Tech Carilion School of Medicine

12:15 pm Lunch Break - Visit with Sponsors/Poster Viewing/Networking

1:00 pm PANEL SESSION: Pathways to Effective Treatments for Traumatic Brain Injury: A Roadmap towards Precision Solutions
Magali Haas, MD, Ph.D., CEO & President, Cohen Veterans Bioscience
Eric Prager, Ph.D., Associate Director External Affairs, Cohen Veterans Bioscience
Lisa Brenner, Ph.D., Vice Chair of Research, Physical Medicine & Rehabilitation, University of Colorado, Anschutz Medical Campus
Allyson Gage, Ph.D., Chief Medical Officer, Cohen Veterans Bioscience
Juliet Haarbauer-Krupa, Ph.D., Senior Health Scientist, TBI Division Injury Prevention, CDC Injury Center
Angela Lumba-Brown, MD, Associate Professor, Neurosurgery & Pediatrics, Stanford University
Mary Jo Pugh, Ph.D., RN, Professor, Department of Medicine, Division of Epidemiology, University of Utah School of Medicine
Douglas H. Smith, MD, Director of PENN'S Center for Brain Injury & Repair, University of Pennsylvania
Elisabeth Wilde, Ph.D., Professor, 
University of Utah

2:00 pm Sex Differences in TBI: from Mice to Men (and Women)

In this presentation, Dr. Harris will share work from her recent review in the Journal of Neurotrauma that summarized findings of sex differences in TBI across animal and human studies (DOI: 10.1089/neu.2018.6171). The analysis of more than 600 studies showed that the largest fraction of human TBI studies reported worse outcomes in females, while more animal TBI studies reported better outcomes in females. Dr. Harris will discuss this discrepancy, and consider ways in which biological sex might interact with TBI severity, age, extracranial injury, and other factors to determine outcome.
Janna Harris, Ph.D., Assistant Professor, University of Kansas Medical Center, Hoglund Biomedical Imaging Center

2:35 pm Conserved Mechanisms Underlying the Benefit of MultiStem Cell Therapy, in Treatment of Acute Injuries of the Central Nervous System
MultiStem cells are an adult adherent allogeneic cellular therapy in Phase 3 clinical trials. CNS injury and disease conditions involve local and peripheral immune system responses to the initial insult. Intravenous (IV) administration of MultiStem cells in the acute time frame after injury provides long term neurological benefit. Mechanism of benefit following MultiStem administration include mitigation of the overt impact of the peripheral immune response, in part originating from the spleen.
Robert (Willie) Mays, Ph.D., Vice President of Regenerative Medicine and Head of Neuroscience Programs, Athersys, Inc.

3:05 pm End of Conference

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