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Wednesday Sessions

Anniversary Lecture 03:  Evolving Concepts of Secondary Injury: Expanding the Therapeutic Window 

Alan Faden, MD;  University of Maryland 

Description

This is the 35th Annual National Neurotrauma Symposium. In celebration of 35 years of exchange of expertise and collaboration, the four founders of the National Neurotrauma Society will each give an anniversary lecture which highlights the past, present, and future of an enduring topic in neurotrauma.

Educational Objectives

  1. Identify the role of reactive oxygen species in the pathology of neurotrauma
  2. Understand evolving concepts of secondary injury and the therapeutic window
  3. Understand how neurotrauma research has advanced over the last decades
PL04: Acute SCI and the Therapeutic Window: Are We Chasing Realistic Targets? 

Sponsored by Craig Neilsen   Moderator: Linda Noble-Haeusslein, PhD; University of Texas at Austin

Panel Discussion:

Description

This session will include a 4 person panel discussion that addresses the following questions:
1) Are current pre-clinical therapeutic windows feasible in the clinical setting?
2) Should we and how do we equate the therapeutic window in animal models to those in humans?
Each of the speakers will briefly answer the above questions from their expert perspective. Following these presentations, we will open up the floor for discussion and debate.

Educational Objectives

  1. Define the acute time period following SCI

  2. Describe and discuss the therapeutic window for targeting therapy after SCI

  3. Discuss ways to increase the therapeutic window after SCI 

Patient Perspective Talk: A Day in the Life with Jeremy Morgan 

Sponsored by uuhc logo   Chair: Gregory Hawryluk, MD, PhD; University of Utah

Description

On the morning of May 23, 2015 Jeremy was struck by a school bus while riding his motorcycle outside of his hometown of Park City, Utah. Jeremy was wearing a helmet at the time of the accident but suffered a series of severe and life threatening injuries, including a traumatic brain injury. Jeremy is a kind hearted young man that has spent his adult years serving his community as a Wild Land Fire Fighter, Volunteer Ski Patroller and Volunteer fire fighter for North Summit County. His charismatic, witty, and selfless personality make Jeremy one of the most loved individuals in his small town. Jeremy and his family will discuss the impact that neurotrauma has on their lives.

Educational Objectives

  1. Observe the impact of neurotrauma from the perspective of the patient
  2. Understand the impact of neurotrauma from the caregiver’s perspective
  3. Discuss recovery milestones after TBI
PL05: Ocular Manifestation of Brain Trauma 

Chairs: Andrew Mayer, PhD; The Mind Research Network & Uzma Samadani, MD; University of Minnesota

  1. Minds Matter: Seeing Concussion Through New Eyes - Christina Master, MD; Children's Hospital of Philadelphia
  2. Vision Rehabilitation for Concussion-Related Vision Disorders - Mitchell Scheiman, PhD; Salus University
  3. Automated Objective Measures of Oculomotor Dysfunction in Concussion - Uzma Samadani, MD; University of Minnesota

Description

This session will cover the interaction of the effects of TBI on the visual system and/or strategies for treatment of ocular dysmotility after brain injury.

Educational Objectives

  1. Understand the complex and inter-related pathology between mild TBI and visual deficits

  2. Review techniques for rehabilitation of concussion-related vision disorders

  3. Discuss automate and objective measures of oculomotor dysfunction after mild TBI

S07: MMPs in CNS: Dual Modulators of Pathology and Regeneration 

Chairs: Alpa Mahuvakar, PhD; UCSF & Josephine Lok, MD; Massachusetts General Hospital

  1. EMMPRIN, Upstream Inducer of MMPs, in CNS Pathology - Deepak Kaushik, PhD; University of Calgary
  2. The Goldilocks Effect: MMPs and Angiogenesis After SCI - Alpa Mahuvakar, PhD; UCSF
  3. MMPs and Post-Traumatic Neuroplasticity: Integrating Multiple Cellular Systems to Reorganize Synapses - Linda Phillips, PhD; VCU

Description

Matrix metalloproteinases (MMPs) are traditionally recognized as inducers of secondary pathogenesis after CNS injury. Recently their complex function and critical balance with inducers and endogenous inhibitors has become more evident. Time-dependent MMP expression after disease and injury exemplifies varied MMP function in wound healing processes such as inflammation, angiogenesis, regeneration, and extracellular matrix modification. In this session, we will evaluate novel MMP molecular interactions in CNS pathology and recovery processes. First, Dr. Wee Yong will present a new approach targeting MMPs via their upstream inducers. EMMPRIN (CD147, Extracellular MMP inducer) is one such physiological inducer and its expression corresponds with that of MMPs. In an animal model of neuroinflammation, antagonizing EMMPRIN reduces leukocyte trafficking and neuropathology. EMMPRIN may constitute a switch whereby its inhibition can alleviate neuroinflammation and injury. Next, Dr. Alpa Mahuvakar will speak about how imbalance of MMPs results in abnormal wound healing after spinal cord injury. Angiogenesis is an important process during wound healing, replenishing the lost blood vessels after spinal cord injury, a critical step in tissue regeneration. Both MMP-2 and MMP-9 play a role in regulating angiogenesis, where an imbalance in the expression of these proteases results in vascular regression and instability. Lastly, Dr. Linda Phillips will discuss novel MMP regulation of synaptic repair after traumatic brain injury. Conventional MMP role in synaptogenesis emphasizes effects on proteins regulating synaptic dissociation, reformation and stabilization. New data show extended MMP integration into inflammatory and vascular pathways which regulate cell signaling and tissue stabilization during injury-induced synapse regeneration.

Educational Objectives

  1. Describe the complex role that MMPs play in pathology of CNS injury

  2. Discuss the mechanisms of MMP-mediated angiogenesis after SCI

  3. Review the mechanisms by which MMPs regulate neuroplasticity after neurotrauma 

S08: Dawn of a New Day: Brain Edema is "Back in the Game" with New Discoveries! 

Chairs: Jerome Badaut, PhD; Institut de Neurosciences Cognitives et Intégratives d’Aquitaine & Andre Obenaus, PhD; Loma Linda University

  1. Water Channels and Brain Edema: Success and Failure - Jerome Badaut, PhD; Institut de Neurosciences Cognitives et Intégratives d’Aquitaine
  2. The Glymphatic System: Role in Post-TBI Edema? - Jeffrey Iliff, PhD
  3. Targeting Substance P to Reduce Edema: TBI vs SCI - Anna Leonard, PhD: University of Adelaide
  4. Vasopressin: A Promising Player for Clinical Edema - Nikolaus Plesnila, PhD; University of Munich

Description

Despite the numerous factors contributing to the high mortality and morbidity associated with traumatic brain injury (TBI), cerebral edema still represents a major predictor for the patient outcome. Despite the excitement following the characterization of the water channels (aquaporin, AQP) in 2000, there are still no treatment(s) directly targeting the AQP. However, the AQP4 are contributing to a new system described in the brain, the glymphatic system contributing in waste clearance. The glymphatic system is of increasing interest in post-TBI edema, as a therapeutic target based on new research. More, recently several outstanding studies have described new molecular and cellular mechanisms for post-TBI edema with the unique potential for development into new therapeutic targets to effectively treat edema. This session will outline the most recent advances in the understanding of mechanisms associated with development of post-traumatic cerebral edema, with a recent advances on vasopressin inhibitors and glibenclamide, as examples of translational research from bench to bedside. It will rejuvenate the most clinically relevant issue, brain edema, unfortunately most frequently forgotten in TBI pre-clinic research.

Educational Objectives

  1. Review the current treatment tools for edema and discuss the promising future therapies for edema
  2. Identify cellular and molecular mechanisms of post-TBI edema
  3. Define and understand glymphatic system in physiology and in the pathology of TBI
S09: Clinical Trial Update: Status and Baseline Demographics for Ongoing Spinal Cord Injury Studies 

Chair: Marco Rizzo, MD: Mayo Clinic & Vertex Pharmaceuticals

  1. Phase 2b/3 SPRING Study: Status & Baseline Demographics - Kee Kim, MD; University of California, Davis
  2. Phase 2/3 RISCIS Study: Status & Baseline Demographics - Michael Fehlings, MD, PhD; University of Toronto
  3. Phase 1 ahSC Study: Status & Baseline Demographics - Kim Anderson-Erisman, PhD; University of Miami
  4. Phase 1/2 AST-OPC1 Study: Status & Baseline Demographics - Edward Wirth, MD, PhD; Asterias Biotherapeutics

Description

This session includes an update on the status of ongoing clinical trials in the cervical spinal cord injury population. Representatives for featured clinical programs will provide background information on mechanism of action and study design before presenting an overview of study status and baseline demographics. The following clinical studies will be featured in this session. The selected trials span the three phases of clinical development and provide insight into acute, subacute, and chronic SCI populations:

• The Phase 2b/3 SPRING study of VX-210 in acute cervical spinal cord injury (NCT02669849)
• The Phase 2/3 RISCIS study of Riluzole in acute cervical spinal cord injury (NCT01597518)
• The Phase 1 study of autologous human Schwann Cells (ahSC) in chronic cervical and thoracic spinal cord injury (NCT02354625)
• The Phase 1/2 study of AST-OPC1 in subacute cervical spinal cord injury (NCT02302157)

This session will provide the spinal cord injury community as a whole with up-to-date insight on the progress of clinical programs for this unmet medical need. Neurotrauma researchers will gain an understanding of the mechanics of clinical development that will help to inform the design of preclinical experimentation and to promote the translation of scientific ideas into feasible development programs.

Educational Objectives

  1. Describe the Current Status of Ongoing SCI Clinical Programs
  2. Design Feasible Development Programs for Translational Research
  3. Design Relevant Preclinical Experimentation
Anniversary Lecture 04  

Wise Young, MD, PhD; Rutgers University

Description

This is the 35th Annual National Neurotrauma Symposium. In celebration of 35 years of exchange of expertise and collaboration, the four founders of the National Neurotrauma Society will each give an anniversary lecture which highlights the past, present, and future of an enduring topic in neurotrauma.

Educational Objectives

  1. Identify the role of reactive oxygen species in the pathology of neurotrauma
  2. Understand evolving concepts of secondary injury and the therapeutic window
  3. Understand how neurotrauma research has advanced over the last decades

Define the acute time period following SCI

2. Describe and discuss the therapeutic window for targeting therapy after SCI

3. Discuss ways to increase the therapeutic window after SCI