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Elucidating the Severity of Preclinical Traumatic Brain Injury Models: A Role for Functional Assessment?

Turner, Ryan C. PhD*,‡; VanGilder, Reyna L. PhD‡,§; Naser, Zachary J. BA*,‡; Lucke-Wold, Brandon P. BS*,‡; Bailes, Julian E. MD‖,¶; Matsumoto, Rae R. PhD‡,¶; Huber, Jason D. PhD‡,¶; Rosen, Charles L. MD, PhD*,‡

doi: 10.1227/NEU.0000000000000292
Research-Laboratory
Press Release

BACKGROUND: Concussion remains a symptom-based diagnosis clinically, yet preclinical studies investigating traumatic brain injury, of which concussion is believed to represent a “mild” form, emphasize histological end points with functional assessments often minimized or ignored all together. Recently, clinical studies have identified the importance of cognitive and neuropsychiatric symptoms, in addition to somatic concerns, following concussion. How these findings may translate to preclinical studies is unclear at present.

OBJECTIVE: To address the contrasting end points used clinically compared with those in preclinical studies and the potential role of functional assessments in a commonly used model of diffuse axonal injury (DAI).

METHODS: Animals were subjected to DAI by the use of the impact-acceleration model. Functional and behavioral assessments were conducted during 1 week following DAI before the completion of the histological assessment at 1 week post-DAI.

RESULTS: We show, despite the suggestion that this model represents concussive injury, no functional impairments as determined by using the common measures of motor, sensorimotor, cognitive, and neuropsychiatric function following injury over the course of 1 week. The lack of functional deficits is in sharp contrast to neuropathological findings indicating neural degeneration, astrocyte reactivity, and microglial activation.

CONCLUSION: Future studies are needed to identify functional assessments, neurophysiologic techniques, and imaging assessments more apt to distinguish differences following so-called “mild” traumatic brain injury in preclinical models and determine whether these models are truly studying concussive or subconcussive injury. These studies are needed not only to understand the mechanism of injury and production of subsequent deficits, but also to rigorously evaluate potential therapeutic agents.

ABBREVIATIONS: ANOVA, analysis of variance

CTE, chronic traumatic encephalopathy

DPBS, Dulbecco's Phosphate-buffered Saline

FJB, Fluoro-Jade B

GFAP, glial fibrillary acidic protein

Iba-1, ionized calcium-binding adapter molecule 1

TBI, traumatic brain injury

*Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, West Virginia;

The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, West Virginia;

§Department of Nursing, West Virginia University School of Medicine, Morgantown, West Virginia;

Department of Neurosurgery, NorthShore University Health System, University of Chicago Pritzker School of Medicine, Evanston, Illinois;

Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, West Virginia

Correspondence: Charles L. Rosen, MD, PhD, Department of Neurosurgery, West Virginia University School of Medicine, One Medical Center Dr, PO Box 9183, Health Sciences Center, Morgantown, WV 26506-9183. E-mail: crosen@hsc.wvu.edu

Received August 28, 2013

Accepted January 03, 2014

Copyright © by the Congress of Neurological Surgeons