Semple group


2021 Semple group. L-R: Mr Erskine Chu, Ms Janet Leung, Dr Sarah Rewell, Mr Rishabh Sharma, Ms Larissa Dill, Dr Bridgette Semple, Ms Tarryn Miles, Ms Larissa Dill, Ms Sadaf Teymornejad

Paediatric Neurotrauma

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Key terms

Neurotrauma, traumatic brain injury, inflammation, epilepsy, animal models, behaviour, paediatric, brain development, myelination

Research Goal

To understand the key biological mechanisms that contribute to poor long-term outcomes after traumatic brain injury, particularly during early childhood

Research Overview

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 brain injury (TBI) to the young brain are poorly understood. Our overall research goal is therefore 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.

Projects

Several ongoing research projects are centred around this theme, using a range of approaches including molecular and cellular methods, neuroimaging, in vivo electroencephalographic recordings, advanced microscopy, and neurobehavioural assays. One of the most commonly reported consequences of paediatric TBI 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 TBI 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 TBI, including the identification of risk and resilience factors, and the contribution of white matter degeneration. In addition, 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 TBI in the mouse, we are evaluating the contribution of key inflammatory cytokines and cellular mediators to seizure susceptibility and aberrant neuroplasticity. We are also exploring the hypothesis that acute immune challenges such as a hospital-acquired infection may perpetuate the development of epilepsy after a brain insult.

See Dr Semple's current projects in SupervisorConnect.

Project Funding

  • 2021-2023 Semple BD, O’Brien TJ and Li J. US Department of Defence Epilepsy Research Program, Idea Development Award. Infections promote post-traumatic epilepsy and poor outcomes after traumatic brain injury.
  • 2018-2020 Semple BD. NHMRC project grant 1122456. Social dysfunction after paediatric brain injury in mice.
  • 2018-2021 Semple BD. NHMRC CDF level 1 1141347. Long-term outcomes after paediatric traumatic brain injury.

Publications

See recent publications for Bridgette Semple in the Monash RSS feed immediately below, at Pubmed and select list further down.

Select publications

Sharma R, Zamani A, Dill LK, Sun M, Chu E, Robinson MJ, O'Brien TJ, Shultz SR, Semple BD. A systemic immune challenge to model hospital-acquired infections independently regulates immune responses after pediatric traumatic brain injury. J Neuroinflammation. 2021 Mar 17;18(1):72. doi: 10.1186/s12974-021-02114-1.PMID: 33731173

Fletcher JL, Dill LK, Wood RJ, Wang S, Robertson K, Murray SS, Zamani A, Semple BD. Acute treatment with TrkB agonist LM22A-4 confers neuroprotection and preserves myelin integrity in a mouse model of pediatric traumatic brain injury. Exp Neurol. 2021 May;339:113652. doi: 10.1016/j.expneurol.2021.113652. Epub 2021 Feb 18.PMID: 33609501

Zamani A, O'Brien TJ, Kershaw J, Johnston LA, Semple BD*, Wright DK* (co-senior authors). White matter changes following experimental pediatric traumatic brain injury: an advanced diffusion-weighted imaging investigation. Brain Imaging Behav. 2021 Jan 7. doi: 10.1007/s11682-020-00433-0. Online ahead of print.PMID: 33411159

Semple BD, O'Brien TJ, Gimlin K, Wright DK, Kim SE, Casillas-Espinosa PM, Webster KM, Petrou S, Noble-Haeusslein LJ. Interleukin-1 Receptor in Seizure Susceptibility after Traumatic Injury to the Pediatric Brain. J Neurosci. 2017 Aug 16;37(33):7864-7877. doi: 10.1523/JNEUROSCI.0982-17.2017. Epub 2017 Jul 19. PMID: 28724747