NNS 2015 Program & Abstract Book

range. In addition, the current evidence supporting various treatment and

management methods of concussion effects is examined, including cog-

nitive restructuring/ reassurance, aerobic therapy, and other therapies.

Return to school and activity will also be reviewed. Reference is made to

the 2013 American Academy of Neurology Sport Concussion evidence-

based guidelines as well as more recent research. Recommendations for

future research is provided to address the existing needs.

Keywords: Sport Concussion, Evidence Based, Concussion As-

sessment, Concussion Management

S08 Operation Brain Trauma Therapy: The Thrill of

Victory and the Agony of Defeat

S08-01

MULTI-CENTER PRE-CLINICAL THERAPY SCREENING IN

TBI: RESULTS OF THE OBTT CONSORTIUM

Patrick Kochanek

Safar Center for Resuscitation Research, Univ. of Pittsburgh, De-

partment of Critical Care Medicine, Pittsburgh, USA

Operation Brain Trauma Therapy (OBTT) is a fully operational, rigorous,

and productive multi-center, pre-clinical drug and circulating biomarker

screening consortium for the field of traumatic brain injury (TBI). In this

presentation, I will synthesize the findings from the first five therapies

tested by OBTT, and discuss both the current work that is ongoing and

potential future directions. Based on the results generated from the first five

therapies tested within the exacting approach used by OBTT, four (nico-

tinamide, erythropoietin, cyclosporine A, and simvastatin) performed be-

low or well below what was expected based on the published literature.

However, OBTT has identified the early post-TBI administration of le-

vetiracetam as a promising agent and has advanced it up the phylogenic

scale to a FPI model in micropigs. The 6th and 7th therapies have just

completed testing (glibenclamide and Kollidon VA 64) and an 8th drug an

aquaporin-4 blocker AER 271 is in testing. The results of those three

therapies will also be updated. Given the concerns related to what has been

described as a reproducibility crisis in basic and pre-clinical research, and

the failures in clinical translation of therapies in TBI, rigorous multi-center,

pre-clinical approaches to therapeutic screening such as OBTT may be

important for the ultimate translation of therapies to the human condition.

Keywords: consortium, reproducibility, behavior, neuropathology,

biomarkers

S08-02

A UNIQUE TOOL FOR CROSS MODEL COMPARISON IN

PRECLINICAL TRAUMATIC BRAIN INJURY

Deborah Shear

Walter Reed Army Institute of Research, Brain Trauma Neuropro-

tection and Neurorestoration Branch, Center for Military Psychiatry

and Neuroscience, Silver Spring, USA

The Operation Brain Trauma Therapy (OBTT) testing platform is

comprised of 4 Drug Screening Centers and a Biomarker Core. Candidate

TBI therapies are first screened across well-established rodent models of

traumatic brain injury (TBI) with the most promising drugs selected for

advanced testing in a micropig animal model (VCU). In this presentation,

I will give an overview of the OBTT approach to primary drug screening

in rodent TBI models to include comparing and contrasting neurobeha-

vioral outcomes specific to each model. The primary OBTT TBI drug

screening models include the fluid percussion injury (FPI) model (Mi-

ami), the controlled cortical impact (CCI) model (U. Pitt.) and the pen-

etrating ballistic-like brain injury (PBBI) model (WRAIR). In addition,

this presentation will illustrate the underlying rationale for combining

neurobehavioral outcomes with neuropathological and biomarker mea-

sures into a scoring matrix to provide comprehensive top-down vs. bot-

tom-up comparisons on each drug. Importantly, for primary drug

screening, unified treatment regimens (tailored to each drug) are em-

ployed across all TBI models and animals are randomly assigned to

treatment vs. control groups with surgeries, behavioral testing and all

subsequent analyses conducted in a blinded fashion within and between

each Center. The strength of this approach is that it provides unprece-

dented rigor to pre-clinical TBI drug research that has been deemed

critical for the successful translation of therapies to clinical studies. This

project is supported by U.S. Army Grant W81XWH-10-1-0623.

Keywords: TBI, OBTT, Neuroprotection, Biomarkers

S08-03

BIOMARKERS AS A WINDOW ON TBI MODELING AND

THERAPEUTIC EFFICACY: RESULTS OF THE OBTT CON-

SORTIUM

Stefania Mondello

University of Messina, Neurosciences, Messina, Italy

Operation Brain Trauma Therapy (OBTT) is a multi-center pre-clin-

ical drug screening consortium testing promising therapies for trau-

matic brain injury (TBI) in 3 well-established TBI models, namely

parasagittal fluid percussion injury (FPI), controlled cortical impact

(CCI), and penetrating ballistic-like brain injury (PBBI) using state-

of-the-art behavioral and histological outcome tools as well as as-

sessing circulating brain damage biomarkers.

In this presentation, I will discuss unique characterization of these

models using novel candidate biomarkers [glial fibrillary acidic protein

(GFAP) and ubiquitin C-terminal hydrolase (UCH-L1)] demonstrating

that different experimental TBI models display specific biomarker

profiles. Furthermore, I will present evidence that drugs differently af-

fect distinct types of lesions as reflected by distinct biomarker pathways

that are also associated with diverse functional deficits and pathological

consequence in brain tissue. These observations indicate that bio-

markers may be a valuable means for characterization, standardization

and refinement of TBI animal models, and serve as surrogate markers of

treatment effect after a specific therapeutic intervention.

In reviewing these concepts, a series of critical issues such as need

for evidence of analytical validity and clinical translation as well as

implications for future research and theranostic roles of biomarkers in

drug discovery and clinical trials will be discussed.

Keywords: Ubiquitin carboxyl-terminal hydrolase-L1, Glial fi-

brillary acidic protein, Fluid percussion injury, Controlled cortical

impact, Penetrating ballistic-like brain injury, Rat

S09 Influence of Lesion, Stress, and Exercise on

Blood Brain Barrier Permeability in the CNS

S09-01

REMOTE BLOOD BRAIN BARRIER DISRUPTION AFTER

MID-THORACIC SPINAL CORD INJURY

D. Michele Basso

, Jonathan Godbout

, Timothy D Faw

, Christopher

N. Hansen

, John F. Sheridan

A-142