Semple Laboratory: Developmental Neurotrauma
|Dr Bridgette Semple||Bridgette.Semple@unimelb.edu.au||+61 3 8344 4108||View page|
Brain injuries in young children often results in debilitating and chronic consequences, including psychosocial and neurocognitive deficits which may persist or emerge as the brain matures. However, the biological mechanisms that underlie poor long-term outcomes following traumatic injury to the young brain are poorly understood. Overall, our research goal is to better understand how the immature brain responds to injury, with a particular focus on the sub-acute and chronic periods after an injury. Ultimately, this knowledge will allow us to develop novel therapeutic interventions aimed at improving outcomes and quality of life for brain-injured patients.
Several ongoing research projects are centred around this theme, using a range of approaches including molecular and cellular methods, neuroimaging, in vivo electroencephalographic recordings, and behavioural assays. Brain injuries are associated with a heightened risk of developing epilepsy, or recurrent seizure activity that may contribute to progressive neurodegeneration and infer with quality of life. Using a validated mouse model of traumatic injury in the paediatric mouse, we are evaluating the contribution of inflammatory mediators (e.g. interleukin-1, high-mobility group box protein) to seizure susceptibility and aberrant neuroplasticity. Neuroplasticity that occurs after a brain injury may contribute to aberrant excitatory circuitry as well as neurocognitive dysfunction, and the potential role of glial phagocytosis in this process is also being investigated.
One of the most commonly reported consequences of paediatric brain injury is a change in social behaviour, for example, a reduction in social interactions, increased social withdrawal and isolation, and associated psychiatric issues such as depression and anxiety. We have developed a model of paediatric brain injury in which mice develop social behaviour deficits as they age to adults, consistent with the trajectory of social behaviour deficits frequently seen in brain-injured children. Using this model, we are now tackling fundamental unanswered questions about the underlying mechanisms of these behavioural changes after brain injury, including the identification of risk and resilience factors.
- Kyria Webster, PhD student
- Mujun Sun, PhD student
- Ann Kim, Honours student
- Thomas McColl, Honours student
- Prof. Terence O'Brien, The University of Melbourne
- Dr. Sandy Shultz, The University of Melbourne
- A/Prof. Leigh Johnston, The University of Melbourne
- A/Prof. Ann Turnley, The University of Melbourne
- Dr. Jerome Staal, Florey Institute of Neuroscience and Mental Health
- Dr. Wah Chin Boon, Florey Institute of Neuroscience and Mental Health
- Dr. Stuart MacDonald, La Trobe University, Melbourne
- Prof. Vicki Anderson, Murdoch Children's Research Institute, Melbourne
- Prof. Marc Seal, Murdoch Children's Research Institute, Melbourne
- Prof. Linda Noble-Hauesslein, The University of California San Francisco, USA
- A/Prof. Susanna Rosi, The University of California San Francisco, USA
- Prof. Anthony Kline, University of Pittsburg, USA
- A/Prof. Cristina Morganti-Kossmann, Monash University, Melbourne
- NHMRC (Early Career Fellowship, 2013-17); The University of Melbourne (Early Career Researcher Grant, 2015-16); Rebecca L Cooper Medical Research Foundation (2016-17).
- Ryan NP, Catroppa C, Godfrey C, Noble-Haeusslein LJ, Shultz SR, O'Brien TJ, Anderson V, Semple BD (2016). Social dysfunction after pediatric traumatic brain injury: a translational perspective. Neurosci Biobehav 64:196-214. doi: 10.1016/j.neubiorev.2016.02.020.
- Hellewell SC, Semple BD and Morganti-Kossmann MC (2015). Therapies negating neuroinflammation after brain trauma, in Special Edition 'Brain Injury and Recovery.' Brain Res pii: S0006-8993(15)00963-4. doi: 10.1016/j.brainres.2015. 12.024.
- Semple BD, Noble-Haeusslein LJ, Gooyit M, Tercovich KG, Peng Z, Nguyen TT, Schroeder VA, Suckow MA, Chang M, Raber J, Trivedi A (2015). Early gelatinase activity is not a determinant of long-term recovery after Traumatic Brain Injury in the immature mouse. PLoS One; 10(11):e0143386. doi: 10.1371/journal.pone. 0143386.
- Semple BD, Lee SM, Sadjadi R, Fritz N, Carlson J, Griep C, Ho V, Jang P, Lamb A, Popolizio B, Saini S, Bazarian JJ, Prins ML, Ferriero DM, Basso M, Noble-Haeusslein LJ (2015). ‘Concussive brain injuries in adolescent athletes – translating clinical and experimental research into perspectives on rehabilitation strategies.’ Front Neurol (Neurotrauma) 6:69. doi: 10.3389/fneur.2015.00069.
- Semple BD, Trivedi A, Gimlin K and Noble-Haeusslein LJ (2015). ‘Neutrophil elastase mediates acute pathogenesis and is a determinant of long-term behavioral recovery after traumatic injury to the immature brain.’ Neurobiol Dis 74:263-80.
- Semple BD, Noble-Hauesslein LJ, Jun Kwon Y, Sam PN, Gibson AM, Grissom S, Brown S, Adahman Z, Hollingsworth CA, Kwakye A, Gimlin K, Wilde EA, Hanten G, Levin HS and Schenk AK (2014). ‘Age-dependent sociosexual and communication deficits after traumatic injury to the developing murine brain.’ PloS One 9(8):e103386.
- Semple BD, Blomgren K, Gimlin K, Ferriero DM and Noble-Haeusslein LJ (2013). ‘Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species.’ Prog Neurobiol 106-107: 1-16.
- Chen CY, Noble-Haeusslein LJ, Ferriero D, Semple BD (2013). Traumatic injury to the immature frontal lobe: ‘A new murine model of long-term motor impairment in the absence of psychosocial or cognitive deficits.’ Dev Neurosci 35: 474-90.
- Semple BD, Canchola SA and Noble-Haeusslein LJ (2012). ‘Deficits in social behaviour emerge during development after paediatric traumatic brain injury in mice.’ J Neurotrauma 29(17): 2672-83.
- Semple BD, Bye N, Ziebell JM and Morganti-Kossmann MC (2010). ‘Deficiency of the chemokine receptor CXCR2 attenuates neutrophil infiltration and cortical damage following closed head injury.’ Neurobiol Dis 40: 394-403.
- Semple BD, Bye N, Rancan M, Ziebell JM and Morganti-Kossmann, MC. (2010) ‘CCL2 in neuroinflammation following traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice.’ J Cereb Blood Flow Metab 30(4):769-82.
- Semple BD, Kossmann T and Morganti-Kossmann MC. (2010) ‘Role of chemokines in CNS health and pathology: a focus on the role of CCL2/CCR2 and CXCL8/CXCR2 networks.’ J Cereb Blood Flow Metab 30(3):459-73.
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For further information about this research, please contact Dr Bridgette Semple