Translational Traumatic Brain Injury Laboratory

Research Overview

Traumatic brain injury (TBI) is a neurodegenerative disease that is induced by forces applied to the brain, and is a common consequence of motor vehicle accidents, slips and falls, and sports and military injuries. TBI is a leading cause of death and morbidity worldwide, and there is no intervention known to improve long-term outcomes in TBI patients. The overall objective of the translational TBI laboratory is to improve our understanding and treatment of this devastating condition. Research projects involve studying the underlying pathophysiological mechanisms of TBI, TBI biomarkers, and potential treatments by utilizing a translational research approach that incorporates both animal models and patients.

A particular research interest  is mild TBI (mTBI), often referred to as concussion. Concussion accounts for the large majority of TBI cases, and is now recognized as a serious medical and societal issue. Of particular concern are individuals at high risk of suffering multiple mTBIs, such as athletes and soldiers, since emerging evidence suggests that repeated mTBIs are associated with long-term neurological consequences and neurodegenerative disease. Unfortunately, it is not known why these long-term effects occur or how they can be prevented. We are currently conducting studies in amatuer and professional athletes, as well as in internationally unique animal models, to provide insight into questions surrounding concussions.

TBI is also associated with the onset of other neurodegenerative diseases including epilepsy, motor neuron disease/amyotrophic lateral sclerosis, and polytrauma. However, the causes and pathophysiological mechanisms of these common conditions, as well as their relationship with TBI, are not well known, nor are there effective interventions for these debilitating diseases. Consequently, there is a great need for these serious medical concerns to be addressed. We have a number of research projects related to the ongoing study of these issues.

Staff

  • Jamie Mayo, Postdoctoral Fellow
  • Shijie Liu, Postdoctoral Fellow
  • David Wright, NIF Fellow, PhD Student
  • Rhys Brady, Research Assistant
  • Lily Taylor, Research Assistant
  • Mujun Sun, PhD Student
  • Xin Tan, PhD Student
  • Ping Zheng, PhD Student
  • Kyria Webster, PhD Student
  • Stefanie Bird, Masters Student
  • Steven Mutimer, Masters Student
  • Thomas McColl, Honours Student
  • Anas Qishta, Honours Student

Collaborators

We collaborate with a number of nationally and internationally recognized scientists and clinicians with expertise relatedto our various projects.

Australia:

  • Dr. Andrew Gardner and Professor Peter Stanwell, University of Newcastle. The use of neuropsychological and MRI biomarkers in professional and amateur collision sport athletes.
  • Professor Andrew Kaye (Department of Surgery), Professor Terence O'Brien (Department of Medicine) & Professor Patricia Desmond (Department of Radiology), The University of Melbourne. Investigating the acute, sub-acute, and chronic effects of concussions in amateur Australian Rules footballers.
  • Dr. Bradley Turner, Florey Neuroscience Institute, The University of Melbourne. Investigating the relationship between TBI and motor neuron disease, and the pathological role of TDP-43.
  • Professor John Hamilton, Department of Medicine, The University of Melbourne. Studying the role of different inflammatory factors in TBI.
  • Dr. Stuart McDonald, Department of Physiology, La Trobe University. Investigating the pathophysiology and treatment of polytrauma.
  • Professors Terence O’Brien, Chris Hovens, and Nigel Jones, The University of Melbourne. Studying the role and treatment of phosphorylated tau in TBI and related neurodegenerative diseases such as epilepsy and chronic traumatic encephalopathy.
  • Professor Leigh Johnston and David Wright, Florey Neuroscience Institutes, University of Melbourne. Developing and examining the use of advanced MRI methods as biomarkers in rodent models of TBI and concussion.
  • Dr. Bridgette Semple, Department of Medicine, The University of Melbourne. Studying the role of inflammation in post-traumatic epilepsy.

USA:

  • Professor Donald Stein, Department of Emergency Medicine, Emory University, USA. We are conducting studies investigating the neuroprotective potental of progesterone, and its derivatives, in TBI and concussion
  • Professor Denes Agoston, Uniformed Services University of Health Sciences, USA. Identifying fluid biomarkers for TBI, concussions, and polytrauma.
  • Prof. Grant Iverson, Harvard University, USA. Examing the long-term effects of concussions and participation in collision sports.

Canada:

  • Professor Brian Christie, The University of Victoria and A/Prof. Richelle Mychysiuk, University of Calgary. Developing, characterizing, and implementing high fidelity rodent models of  concussion.

Funding

  • Australian National Health and Medical Research Council (NHMRC)
  • The Motor Neurone Disease Research Institute of Australia (MNDRIA)
  • The Melbourne Neuroscience Institute  
  • The University of Melbourne

Research Publications

  1. Tan XL, Wright DK, Liu S, Hovens C, O'Brien TJ, Shultz SR. Sodium selenate, a
    protein phosphatase 2A activator, mitigates hyperphosphorylated tau and improves
    repeated mild traumatic brain injury outcomes. Neuropharmacology. 2016 May
    7;108:382-393. doi: 10.1016/j.neuropharm.2016.05.001. [Epub ahead of print]
    PubMed PMID: 27163189.
  2. McDonald SJ, Sun M, Agoston DV, Shultz SR. The effect of concomitant
    peripheral injury on traumatic brain injury pathobiology and outcome. J
    Neuroinflammation. 2016 Apr 26;13(1):90. doi: 10.1186/s12974-016-0555-1. Review.
    PubMed PMID: 27117191; PubMed Central PMCID: PMC4847339.
  3. Ryan NP, Catroppa C, Godfrey C, Noble-Haeusslein LJ, Shultz SR, O'Brien TJ,
    Anderson V, Semple BD. Social dysfunction after pediatric traumatic brain injury: A translational perspective. Neurosci Biobehav Rev. 2016 May;64:196-214. doi:10.1016/j.neubiorev.2016.02.020. Epub 2016 Mar 3. Review. PubMed PMID: 26949224.
  4. Webster KM, Wright DK, Sun M, Semple BD, Ozturk E, Stein DG, O'Brien TJ,
    Shultz SR. Progesterone treatment reduces neuroinflammation, oxidative stress and brain damage and improves long-term outcomes in a rat model of repeated mild traumatic brain injury. J Neuroinflammation. 2015 Dec 18;12:238. doi:
    10.1186/s12974-015-0457-7. PubMed PMID: 26683475; PubMed Central PMCID:
    PMC4683966.
  5. Gardner AJ, Iverson GL, Quinn TN, Makdissi M, Levi CR, Shultz SR, Wright DK,
    Stanwell P. A preliminary video analysis of concussion in the National Rugby
    League. Brain Inj. 2015 Jun 17:1-4. [Epub ahead of print] PubMed PMID: 26083052.
  6. Shultz SR, Sun M, Wright DK, Brady RD, Liu S, Beynon S, Schmidt SF, Kaye AH,
    Hamilton JA, O'Brien TJ, Grills BL, McDonald SJ. Tibial fracture exacerbates
    traumatic brain injury outcomes and neuroinflammation in a novel mouse model of
    multitrauma. J Cereb Blood Flow Metab. 2015 Aug;35(8):1339-47. doi:
    10.1038/jcbfm.2015.56. Epub 2015 Apr 8. PubMed PMID: 25853909; PubMed Central
    PMCID: PMC4528010.
  7. Shultz SR, Wright DK, Zheng P, Stuchbery R, Liu SJ, Sashindranath M, Medcalf
    RL, Johnston LA, Hovens CM, Jones NC, O'Brien TJ. Sodium selenate reduces
    hyperphosphorylated tau and improves outcomes after traumatic brain injury.
    Brain. 2015 May;138(Pt 5):1297-313. doi: 10.1093/brain/awv053. Epub 2015 Mar 13.
    PubMed PMID: 25771151.
  8. Johnstone VP, Wright DK, Wong K, O'Brien TJ, Rajan R, Shultz SR. Experimental
    Traumatic Brain Injury Results in Long-Term Recovery of Functional Responsiveness in Sensory Cortex but Persisting Structural Changes and Sensorimotor, Cognitive, and Emotional Deficits. J Neurotrauma. 2015 Sep 1;32(17):1333-46. doi:10.1089/neu.2014.3785. Epub 2015 May 14. PubMed PMID: 25739059.
  9. Brady RD, Shultz S, Sun M, Romano T, van der Poel C, Wright DK, Wark JD,
    O'Brien TJ, Grills BL, McDonald SJ. Experimental traumatic brain injury induces
    bone loss in rats. J Neurotrauma. 2015 Feb 16. [Epub ahead of print] PubMed PMID:
    25686841.
  10. Johnstone VP, Shultz SR, Yan EB, O'Brien TJ, Rajan R. The acute phase of mild
    traumatic brain injury is characterized by a distance-dependent neuronal
    hypoactivity. J Neurotrauma. 2014 Nov 15;31(22):1881-95. doi:
    10.1089/neu.2014.3343. Epub 2014 Sep 11. PubMed PMID: 24927383; PubMed Central
    PMCID: PMC4224042.
  11. Dedeurwaerdere S, Shultz SR, Federico P, Engel J Jr. Workshop on Neurobiology of Epilepsy appraisal: new systemic imaging technologies to study the brain in experimental models of epilepsy. Epilepsia. 2014 Jun;55(6):819-28. doi:10.1111/epi.12642. Epub 2014 May 16. PubMed PMID: 24836499; PubMed Central PMCID:PMC4057947.
  12. Shultz SR, O'Brien TJ, Stefanidou M, Kuzniecky RI. Neuroimaging the
    epileptogenic process. Neurotherapeutics. 2014 Apr;11(2):347-57. doi:
    10.1007/s13311-014-0258-1. Review. PubMed PMID: 24488707; PubMed Central PMCID:
    PMC3996128.
  13. Shultz SR, Tan XL, Wright DK, Liu SJ, Semple BD, Johnston L, Jones NC, Cook
    AD, Hamilton JA, O'Brien TJ. Granulocyte-macrophage colony-stimulating factor is
    neuroprotective in experimental traumatic brain injury. J Neurotrauma. 2014 May
    15;31(10):976-83. doi: 10.1089/neu.2013.3106. Epub 2014 Mar 7. PubMed PMID: 24392832; PubMed Central PMCID: PMC4012635.
  14. Zheng P, Shultz SR, Hovens CM, Velakoulis D, Jones NC, O'Brien TJ.
    Hyperphosphorylated tau is implicated in acquired epilepsy and neuropsychiatric
    comorbidities. Mol Neurobiol. 2014 Jun;49(3):1532-9. doi:10.1007/s12035-013-8601-9. Epub 2013 Dec 10. Review. PubMed PMID: 24323428.
  15. Shultz SR, Cardamone L, Liu YR, Hogan RE, Maccotta L, Wright DK, Zheng P, Koe A, Gregoire MC, Williams JP, Hicks RJ, Jones NC, Myers DE, O'Brien TJ, Bouilleret V. Can structural or functional changes following traumatic brain injury in the rat predict epileptic outcome? Epilepsia. 2013 Jul;54(7):1240-50. doi:10.1111/epi.12223. Epub 2013 May 29. PubMed PMID: 23718645; PubMed Central PMCID: PMC4032369.