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Medicine

A Repetitive Concussive Head Injury Model in Mice

Published: October 12th, 2016

DOI:

10.3791/54530

1Program for Neurotrauma, Neuroproteomics & Biomarkers Research, University of Florida, 2Department of Psychiatry, University of Florida, 3Department of Neuroscience, University of Florida

Concussion presents the most common type of traumatic brain injury. Therefore, a repetitive concussive animal model, which replicates the important features of an injury in patients, may provide a means to study concussion in a rigorous, controlled, and efficient manner.

Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.

Concussion, also called mild traumatic brain injury (mTBI), is the most frequent occurrence of traumatic brain injury (TBI) and affects millions of people in United States. Concussions can be tricky to diagnose and there is no specific cure for concussion. There is a growing recognition and some evidence that mild mechanical trauma resulting from sports injuries, military combat, and other physically engaging pursuits may have cumulative and chronic neurological consequences1,2. However, there is still a lack of knowledge regarding concussions and their effects. Current methodology restricts the studies of pathology and treatment in humans since only neurol....

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All procedures were performed under protocols #201207692 approved by the Institutional Animal Care and Use Committee of University of Florida and in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

1. Animal Care

  1. Use 3–4-month-old male C57BL/6J mice. Provide bedding, nesting material, food, and water ad libitum. Keep the mice in ambient temperatures controlled at 20 - 22 °C with constant 12-hr light/12-hr dark c.......

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In this model (Figure 1 A-C), there were brief periods of gasping and shallow respirations. A loss of consciousness (unconscious) is defined as a decrease in the breathing rate or transient termination of breathing before resuming a normal respiration. An impact on the center of the head caused short-term unconsciousness (7.5 ± 4.7, 7.8 ± 5.5, 10.2 ± 8.8, 9.5 ± 8.0 sec at each impact separately, Figure 1D). Mouse brains showed normal m.......

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To mimic brain injuries morphologically similar to the clinical condition, post-concussion symptoms are expected. Post-concussion symptoms generally include headaches, dizziness, vertigo, fatigue, memory and sleeping problems, trouble concentrating as well as anxiety, and depressed mood. Since somatic symptoms may not yet be measurable in animal models, the changes of motor and cognitive function and emotional behavior are used as criteria for rationally evaluating concussion in animal models. In a previous reported stud.......

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This works was supported by funding from a Florida Health grant (Brain and spinal cord injury research fund) (KKW).

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Name Company Catalog Number Comments
anesthesia machine Eagle Eye Anesthesia, Inc Model 150  anesthesia
Electromagnetic Impactor LeicaBiosystems Impact One Stereotaxic Impactor perform impaction
Digital Stereotaxic instrument LeicaBiosystems 39462501 mount mouse and positioning tips
Sicilone rubber-coated metal tip Precision Tool & Engineering, Gainesvill FL custom-made impact tip
Lithium Ion All-in-One Trimmer WAHL Home Products 9854-600 shave mouse hair
paper clips custom-made probe tip
Cotton tipped applicators MEDLINE MDS202055 scrub head with saline
Tissue Tek O.C.T. ASKURA FINETEK USA INC 4583 tissue embedding
anti-GFAP Dako CA93013 antibody for IHC
anti Ferritin Sigma F6136 antibody for IHC
VECTASTAIN Elite ABC  kit Vector laboratories PK-6100 IHC detection system
Permount Mounting Medium Fisher Scientific SP15-100
Aperio XT ScanScope scanner Leica Microsystems Inc, slides scanning
Leica AutoStainer XL Leica the pathology Company ST2010 H&E staining
DAB  sigma D3939 IHC detection system

  1. Baugh, C. M., et al. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav. 6 (2), 244-254 (2012).
  2. McKee, A. C., et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J. Neuropathol Exp Neurol. 68 (7), 709-735 (2009).
  3. Petraglia, A. L., Dashnaw, M. L., Turner, R. C., Bailes, J. E. Models of mild traumatic brain injury: translation of physiological and anatomic injury. Neurosurgery. 75 Suppl (4), S34-S49 (2014).
  4. Goldstein, L. E., McKee, A. C., Stanton, P. K. Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy. Alzheimers Res Ther. 6 (5), 64 (2014).
  5. Gold, E. M., et al. Functional assessment of long-term deficits in rodent models of traumatic brain injury. RegenMed. 8 (4), 483-516 (2013).
  6. Xiong, Y., Mahmood, A., Chopp, M. Animal models of traumatic brain injury. Nat Rev Neurosci. 14 (2), 128-142 (2013).
  7. Luo, J., et al. Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury. Front Neurol. , 5-12 (2014).
  8. Yang, Z., et al. Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model. Sci Rep. 10 (5), 11178 (2015).
  9. Zhang, J., et al. Inhibition of monoacylglycerol lipase prevents chronic traumatic encephalopathy-like neuropathology in a mouse model of repetitive mild closed head injury. J Cereb Blood Flow Metab. 35 (3), 443-453 (2015).
  10. Petraglia, A. L., et al. The spectrum of neurobehavioral sequelae after repetitive mild traumatic brain injury: a novel mouse model of chronic traumatic encephalopathy. J Neurotrauma. 31 (13), 1211-1224 (2014).
  11. Lumpkins, K. M., Bochicchio, G. V., Keledjian, K., Simard, J. M., McCunn, M., Scalea, T. Glial fibrillary acidic protein is highly correlated with brain injury. J Trauma. 65 (4), 778-782 (2008).
  12. Yang, Z., Wang, K. K. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 38 (6), 364-374 (2015).
  13. Liu, H., et al. Increased expression of ferritin in cerebral cortex after human traumatic brain injury. Neurol Sci. 34 (7), 1173-1180 (2013).
  14. Jordan, B. D., et al. The clinical spectrum of sport-related traumatic brain injury. Nat Rev Neurol. 9 (4), 222-230 (2013).

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