Functional and Molecular Correlates after Single and Repeated Rat Closed-Head Concussion: Indices of Vulnerability after Brain Injury

Andrea Mountney*, Angela M. Boutté, Casandra M. Cartagena, William F. Flerlage, Wyane D. Johnson, Chanyang Rho, Xi Chu Lu, Angela Yarnell, Sean Marcsisin, Jason Sousa, Chau Vuong, Victor Zottig, Lai Yee Leung, Ying Deng-Bryant, Janice Gilsdorf, Frank C. Tortella, Deborah A. Shear

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Closed-head concussive injury is one of the most common causes of traumatic brain injury (TBI). Isolated concussions frequently produce acute neurological impairments, and 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. 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 noninvasive closed-head impact model that 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 neurological impairments with sustained astrogliosis and white matter thinning. Acute changes in molecular signatures correlated with behavioral impairments, whereas increased times to regaining 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 neuropathological 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.

Original languageEnglish
Pages (from-to)2768-2789
Number of pages22
JournalJournal of Neurotrauma
Volume34
Issue number19
DOIs
StatePublished - 1 Oct 2017
Externally publishedYes

Keywords

  • CatWalk
  • GFAP
  • Neurobehavioral Severity Scale-Revised
  • ataxia
  • chronic traumatic encephalopathy
  • concussion
  • mild TBI
  • quantitative electroencephalography
  • rodent gait
  • tau

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