Citation

Mountney A, Boutte A, Cartagena CM, Flerlage WJ, Johnson D, Rho C, Lu XM, Yarnell AM, Marcsisin SR, Sousa J, Vuong C, Zottig VE, Leung LY, Deng-Bryant Y, Gilsdorf J, Tortella FC, Shear DA. J. Neurotrauma 2017; 34(19): 2768-2789.

Affiliation

Walter Reed Army Institute of Research, Branch of Brain Trauma Neuroprotection and Neurorestoration , Silver Spring, Maryland, United States ; deborah.a.shear.civ@mail.mil.

Copyright

(Copyright © 2017, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2016.4679

PMID

28326890

Abstract

Closed-head concussive injury is one of the most common causes of traumatic brain injury (TBI). Isolated concussions frequently produce acute neurological impairments; however, individuals typically recover spontaneously within a short time frame. In contrast, brain injuries resulting from multiple concussions can result in cumulative damage and elevated risk of developing chronic brain pathologies, including chronic traumatic encephalopathy (CTE). Increased attention has focused on identification of diagnostic markers that can prognostically serve as indices of brain health after injury, revealing the temporal profile of vulnerability to a second insult. Such markers may demarcate adequate recovery periods before concussed patients can return to required activities. We developed a non-invasive closed-head impact model which captures the hallmark symptoms of concussion in the absence of gross tissue damage. Animals were subjected to single or repeated concussive impact and examined using a battery of neurological, vestibular, sensorimotor, and molecular metrics. A single concussion induced transient, but marked acute neurological impairment, gait alterations, neuronal death, and increased glial fibrillary acidic protein (GFAP) expression in brain tissue. As expected, repeated concussions exacerbated sensorimotor dysfunction, prolonged gait abnormalities, induced neuroinflammation, and upregulated GFAP and Tau. These animals also exhibited chronic functional neurologic impairments with sustained astrogliosis and white matter thinning. Acute changes in molecular signatures correlated with behavioral impairments; while, increased times to regain consciousness and balance impairments were associated with higher GFAP and neuroinflammation. Overall, behavioral consequences of either single or repeated concussive impact injuries appeared to resolve more quickly than the underlying molecular, metabolic and neuropathologic abnormalities. This observation, which is supported by similar studies in other mTBI models, underscores the critical need to develop more objective prognostic measures for guiding return-to-play decisions.

Language: en

Keywords

BEHAVIORAL ASSESSMENTS; BIOMARKERS; EEG; INFLAMMATION; TRAUMATIC BRAIN INJURY