The Young Investigator TBI Virtual Summer Conference

JUNE 29, 2021

The producers of the Annual Traumatic Brain Injury Conference are organizing a brand new event entitled “The Young Investigator TBI Virtual Summer Conference.” This new one-day event will showcase emerging brain injury research from early-career scientists, such as graduate students, post-docs and new academic faculty appointees.

Topic areas include:

  • Imaging/Biomarkers
  • Outcomes research
  • Diagnostics
  • Basic science
  • Preclinical research
  • Clinical research

We are offering a $500 award for the best original research, to be decided on by a panel of pre-eminent brain injury researchers. The winner of this award will also be invited to speak at our 11th Annual Traumatic Brain Injury Conference, which is taking place on October 4-5, 2021 in Washington, DC.

REGISTRATION IS NOW OPEN FOR THIS FREE EVENT. CLICK ON THE TAB BELOW TO REGISTER.

   Christina Acosta, Graduate Student, LSU Health Sciences Center Shreveport

   Mehwish Anwer, MPhil, Ph.D.
, Postdoctoral Research Fellow, University of British Columbia

   Nayoung Kim, Ph.D.
, Postdoctoral Associate, Weill Cornell Medicine

.  Jesse Lai, Ph.D.
, Postdoc, University of Southern California

   Sara Mithani, Ph.D.
, Postdoctoral Fellow, NINR, NIH

   Zachary Riggenbach
, Medical Student, Uniformed Services University of the Health Science

   Min-Kyoo Shin, Ph.D.
, Senior Research Associate, Case Western Reserve University

   Edwin Vazquez-Rosa, Ph.D.
, Senior Research Associate, Case Western Reserve University

   Fabio Vigil, Ph.D.
, Postdoctoral Fellow, University of Texas Health San Antonio

   Laura Villasana, Ph.D.
, Assistant Professor, Oregon Health Sciences University


June 29, 2021

9:30 am CDT Cluster Analysis Fails to Reveal mTBI Symptom Phenotype
This talk will discuss results from an mTBI hierarchical clustering analysis. Data was collected as a part of the Warrior Strong study, a survey database from Soldiers recently returning home from deployment. The main objective of the analysis was to determine specific mTBI phenotypes among survey respondents who self-reported a history of mTBI. What this analysis found, however, was that no unique phenotype exists among mTBI respondents. There were no clusters that had a predominantly somatic/sensory, cognitive, or affective response. Instead, clusters were grouped based on their symptom severity across all symptom domains. This result seems to oppose recently published analysis on mTBI phenotypes and offers caution when planning long-term mTBI research based on the presence of such phenotypes.
Zachary Riggenbach, Medical Student, Uniformed Services University of the Health Science

10:00 am CDT Objective Neurophysiological Markers of Cognitive Recovery Following Pediatric Acquired Brain Injury
Cognitive impairment is the most persistent and distressing sequela in survivors of brain injury. In adults, objective neuroimaging measures to support diagnosis and prognosis were recently endorsed by AAN practice guidelines. Equivalent objective measures have not been established in children—an especially great challenge due to the combined heterogeneity of both brain injury and pediatric development. To determine whether objective neuroimaging measures can be employed to diagnose, detect and track cognitive function following pediatric brain injury. In a convenience sample of 44 children with and without brain injury, we demonstrate that neurophysiological measures of sensory processing, orienting attention and imagined action can track recovery and identify covert cognitive abilities. Our direct measurements of brain activity reveal features of cognitive recovery that transcend both the heterogeneity of brain injury and the variation across different stages of brain development. To improve diagnosis and prognosis of cognitive recovery and track response to therapies, such markers should be employed in children.
Nayoung Kim, Ph.D., Postdoctoral Associate, Weill Cornell Medicine

10:30 CDT Elevated Phosphorylated Tau Following a Sports Concussion: Findings from the NCAA and Department of Defense CARE Consortium
Every year, millions of athletes in the United States sustain a sport-related concussion (SRC), yet the diagnosis and care provided are limited by our understanding of biological changes that occur following brain trauma. Recent evidence suggests that neuroinflammatory cytokines exacerbate and positively correlate with tau pathology, causing tau hyperphosphorylation, aggregation, and neurodegeneration. Moreover, accumulation of phosphorylated tau (pTau) causes synaptic impairment, neuronal dysfunction and is a key pathological feature of several neurodegenerative diseases. The objective of this study was to understand pTau-181 protein concentration in athletes with SRC. A total of 161 collegiate athletes with (n=140) and without (n=21) SRC had blood collected within 48 hours of injury. Plasma samples were analyzed in duplicate using the Single Molecule Array pTau-181 advantage V2 assay kit. Our findings indicate pTau-181 are altered after acute SRC and this shows early promise as a biomarker of acute concussion.
Sara Mithani, Ph.D., Postdoctoral Fellow, NINR, NIH

11:00 am CDT Reducing Acetylated-tau is Neuroprotective in Brain Injury
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

11:30 am CDT A Concussive Injury Compromises the Neurogenic Response to a Subsequent Head Injury
In response to traumatic brain injury (TBI), neural stem cells (NSCs) undergo robust proliferation increasing the generation of new neurons (neurogenesis) within the hippocampus, a brain region critical for learning and memory. Because new neurons integrate and develop properties similar to mature neurons, post-traumatic neurogenesis is thought to contribute to hippocampal recovery. Paradoxically however, TBI also leads to long-term impairments in neurogenesis, potentially leaving the hippocampus deficient in this putative repair mechanism. Recent experiments in our lab with mice demonstrate that a mild form of TBI that is similar to a concussive injury impairs cellular proliferation and the neurogenic response to a subsequent similar injury, even when the second injury occurs 2 months later. In accord with previous findings, we observe that the proliferation of the NSCs after the second injury is reduced, suggesting TBI increases the quiescence of NSCs. These studies have important implications for cognitive recovery from a repeated TBI and may present a therapeutic strategy to mitigate hippocampal dysfunction following a head injury.
Laura Villasana, Ph.D., Assistant Professor, Oregon Health & Science University

12:00 pm CDT Lunch Break

1:00 pm CDT 3D Molecular Mapping and Spatial Gene Expression: New avenues for advancing TBI research
Traumatic brain injury (TBI) can lead to chronic neuropsychological impairments including post-traumatic stress disorder (PTSD) and can also result in increased risk of dementias such as Alzheimer’s Disease (AD). The overall goal of my research is to investigate the molecular pathways that are affected by TBI, and modulated by amyloid β, and to determine how they relate to PTSD-like behavioral changes. In this talk, Dr. Anwer will discuss the use of cutting-edge technologies such as Visium Spatial gene expression, single cell RNA sequencing and tissue clearing in advancing our knowledge of molecular mechanisms that lead to development of PTSD and AD after TBI. She will also share her on-going work on generation of 3D maps of TBI-induced neuronal activity in cleared brain tissue and use of ARIVIS for 3D image analysis.
Mehwish Anwer, MPhil, Ph.D., Postdoctoral Research Fellow, University of British Columbia

1:30 pm CDT A Novel Route to Neuroprotection in Chronic Traumatic Brain Injury
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., Senior Research Associate, Case Western Reserve University

2:00 pm CDT Preclinical and Mechanistic Study of the Acute and Long-term Beneficial Effects of Kv7 Current Augmentation After a Traumatic Brain Injury
Kv7 voltage-gated K+ channels underlie the neuronal “M-current,” which plays a dominant role in control over neuronal excitability. Thus, Kv7 “opener” drugs have been developed as anti-convulsant. We have recently shown, using the controlled closed cortical impact traumatic brain injury (TBI) mouse model, that one acute dose of the prototypic Kv7 opener, retigabine (RTG), reduces TBI-induced post-traumatic seizures, cellular metabolic stress, cell death, and inflammatory response. To move towards clinical trials, we have performed dose-response experiments and investigated the biological mechanisms of the beneficial effects of Kv7 current augmentation. Our results support pharmacological Kv7 current augmentation as an effective post-TBI treatment, providing ameliorative effects that can last for years and go beyond the reduction of neuronal hyperexcitability. RTG is an FDA-approved antiepileptic drug, which facilitates its use as a post-TBI treatment.
Fabio Vigil, Ph.D., Postdoctoral Fellow, University of Texas Health San Antonio

2:30 pm CDT A CRISPR Interference Screen in iPSC-derived Cerebral Organoids Identifies Novel Therapeutic Targets for Traumatic Brain Injury
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., Postdoc, University of Southern California

3:00 pm CDT A Role for PRMT7 Post-repetitive and Mild Traumatic Brain Injury
Our data suggests a novel role for PRMT7 (protein arginine methyltransferases) in the disease progression as indicated by the significant temporal decrease post-repetitive and mild TBI (rmTBI). PRMTs are novel targets that catalyze the methylation of arginine residues involved in transcription, translation, receptor trafficking, and protein stability. There are currently 11 known PRMT isoforms (PRMT1-11)5, with PRMT7 gene deletion in human patients causing developmental and neurological deficits such as intellectual disability, microcephaly, and brachydactyly, along with hyperexcitability and impaired social behaviors in murine in vivo models. Given the clinical translation of PRMT7 in human patients in conjunction with our data, our main goal is to elucidate the extent in which PRMT7 mediates neuronal hyperexcitability, blood brain barrier (BBB) permeability, and behavioral deficits post-mTBI. Our central hypothesis is that the loss of PRMT7, due to repetitive and mild traumatic brain injury, leads to blood brain barrier (BBB) permeability, exacerbates excitotoxicity, and contributes to behavioral deficits.
Christina Acosta, Graduate Student, LSU Health Sciences Center Shreveport

3:30 pm CDT End of Conference
Please click on the following button to register for this free event.
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BRAINBox Solutions™ multi-modality approach is led by the leaders in the industry. It will include blood biomarker panels available on a point of care instrument and standard laboratory systems, as well as neurocognitive testing, to provide objective evidence of injury and prediction of patient recovery. Other relevant modalities will continue to be assessed.
If you'd like to receive information regaridng sponsorship opportunities for this event, please email us at enquries@tbiconference.com.

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