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Modeling of Traumatic Brain Injury and its Implications in Studying the Pathology of Repeated Mild Impacts to the Head

  • Michael J. Kane
  • Mariana Angoa Pérez
  • Denise I. Briggs
  • David C. Viano
  • Christian W. Kreipke
  • Donald M. Kuhn
Chapter

Abstract

Traumatic brain injury (TBI) results from a blow to the head and can range in severity from mild to severe. Mild TBI is the most common form of head injury and constitutes about 80–90 % of all cases. Repetitive mild TBI (rmTBI) has emerged as a significant public health concern as the number of individuals experiencing this type of injury in military combat operations and in athletic endeavors continues to increase at a very high rate. The medical and scientific communities have only just started to grapple with its complexity and are struggling to understanding the underlying pathotrajectory and to develop and implement tests to detect and assess rmTBI. For the most part, routine imaging approaches and standard neuropsychological tests contribute little to the evaluation and management of rmTBI. A better understanding of the pathological consequences of rmTBI, including elucidating the role of hypoperfusion, could be achieved with a validated animal model, but most existing models impart acute injuries that are severe and do not simulate the essential characteristics of head impacts that are known to result in mild concussion in humans. Here we discuss several current models of head trauma in the context of strengths and weaknesses of using these models. We also include a discussion of a new model of rmTBI that involves a blow to the unrestrained head of a mouse. Upon each impact, the subject’s head undergoes rapid acceleration. After as many as five to ten head impacts, mice recover consciousness rapidly and show no signs of skull fracture, edema, intracranial bleeding, or seizure activity. Histological signs of injury include glial activation and a delayed development of tangle-like proteins as seen in human chronic traumatic encephalopathy. This new model closely simulates head impact as seen in humans who experience rmTBI. Initial experimental validation suggests that the pathotrajectory is also very similar to histological signs observed in postmortem human brain from individuals who had sustained rmTBI. Future studies using this new model will hopefully uncover new mechanisms that underlie dysfunctional blood flow and metabolism and, more importantly, the cognitive and behavioral deficits associated with rmTBI.

Keywords

Traumatic Brain Injury Blast Wave Severe Traumatic Brain Injury Skull Fracture Mild Traumatic Brain Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Michael J. Kane
    • 1
    • 2
  • Mariana Angoa Pérez
    • 1
    • 2
  • Denise I. Briggs
    • 1
    • 2
  • David C. Viano
    • 3
    • 4
  • Christian W. Kreipke
    • 2
  • Donald M. Kuhn
    • 1
    • 2
  1. 1.Department of Psychiatry and Behavioral NeurosciencesWayne State University School of MedicineDetroitUSA
  2. 2.John D. Dingell VA Medical Center, Research and Development ServiceDetroitUSA
  3. 3.ProBiomechanics LLCBloomfield HillsUSA
  4. 4.Department of Biomedical Engineering, School of EngineeringWayne State UniversityDetroitUSA

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