23 Oct 2021

New international collaboration to drive clinical translation for traumatic brain injury in young children

L-R: Dr Bridgette Sempleand Professor Ramesh Raghupathi

Preventive and targeted drug therapies have great potential to improve the lasting social behavioural problems that occur in young children following a traumatic brain injury. 

A mini-review authored by Dr Bridgette Semple, Department of Neuroscience, Monash University and Professor Ramesh Raghupathi, Department of Neurobiology and Anatomy, College of Medicine, Drexel University, has pulled together the limited, but emerging pre-clinical studies which show that there are promising benefits on social functioning following a traumatic brain injury (TBI) in early childhood.

The mini-review features as part of a research topic focused on the Long-Term Consequences of Pediatric Traumatic Brain Injury in the peer-reviewed journal Frontiers in Neurology (Neurotrauma), also edited by Dr Semple, Professor Raghupathi and Dr Jimmy Huh.

Social behaviour outcomes, an indication of social functioning, are used to assess persisting or lasting social deficits that arise as a result of TBI. Social functioning involves many different components that provide a person with the ability to appropriately take in social information from their environment or surroundings and use this to interact and communicate with others to contribute to daily living, the community and wider society. However, damaging this functioning, as happens following a TBI, has a huge impact on those affected.

This is particularly challenging for young children whose brains are still undergoing development and the maturation process. This developmental setting creates considerable setbacks and disability that worsen children’s quality of life and their maturation into adolescence and adulthood. Young children may in fact fare worse following TBI compared to older children or adults, having a significant propensity for social behavioural deficits. Adding further complexity to the development of potential treatment strategies is the diverse range of the severity and nature of social deficits.

The mainstay of treatment at present focuses on rehabilitative care to manage the cognitive and functional issues following paediatric traumatic brain injury. Studies that investigate drug therapies to treat social deficits are scarce but are promising in their effectiveness and being added as a complement to rehabilitation.

TBI is the leading cause of mortality and morbidity in young children in developed countries, particularly those under the age of five. Most injuries are due to the child falling over, with motor vehicle accidents and “non-accidental injury” (also known as “shaken baby syndrome”) among other causes.

Children who experience TBI face poor outcomes later in life, mostly cognitive problems associated with learning and memory, and also social problems such as isolation, and difficulty in forming friendships and relationships, Dr Semple said.

“These outcomes can develop many years after the injury, the results of progressive damage that’s happening over time. We think that inflammation is one of several processes that contributes to that progressive damage”

TBI in children is now treated in essentially the same way as adults, through medical management to try and prevent excessive swelling in the brain. However, research into TBI aimed at improving treatment was mostly focussed on adults, Dr Semple said. “We’re really just starting to understand that that may not always be applicable to the developing brain.”

Dr Semple and Professor Raghupathi drew together the emerging literature on how social behaviour after early life brain trauma can be manipulated in experimental models in their mini-review. "We hope that we can encourage further research in the field to drive and accelerate clinical translation."

Earlier this year, Dr Semple published results of a study that showed preventive treatment with a novel compound, LM22-A, was able to protect the brain from degeneration after an early-life brain injury (see blog story). 

Recent research from Professor Raghupathi's laboratory using targeted intranasal oxytocin treatment reduced and improved problems in social interactions after a rat model of paediatric TBI. "The significance of these observations lies in the fact that we were able to regulate the activity of the brain regions that control social behaviour using oxytocin, akin to what has been demonstrated in Autism Spectrum Disorders," said Professor Raghupathi.

Paediatric rodent models of TBI have been shown to result in similar neurobehavioural consequences to those seen in young patients after a TBI. "My group, and the Raghupathi lab, have independently conducted much of the foundational work in this field, demonstrating that experimental models of paediatric brain trauma recapitulate social behaviour problems that are commonly seen after brain injury in young children," Dr Semple said. Professor Raghupathi agreed.

"It is exciting that the social behaviour deficits can be observed in multiple species and in different models of paediatric TBI. This sets up the groundwork for truly translational research."

The review marks a new collaborative partnership between Professor Raghupathi and Dr Bridgette Semple, as they collectively seek funding to work together in the near future. Professor Raghupathi will be an international guest speaker in the Department of Neuroscience’s Translational Seminar Series, later this year on Monday 6 December, 12:30 - 1:30pm - save the date!

Source

Semple BD, Raghupathi R. A Pro-social Pill? The Potential of Pharmacological Treatments to Improve Social Outcomes After Pediatric Traumatic Brain Injury. Front Neurol. 2021 Aug 19;12:714253. doi: 10.3389/fneur.2021.714253

22 Oct 2021

12-18 Oct 2021 Central Clinical School recent publications

What do innate lymphoid cells do in chronic respiratory diseases?
Margaret Hibbs led review (Frontiers in Immunology) explains
Recent publications featuring research as notified by PubMed during 12-18 Oct 2021 from Central Clinical School affiliated researchers in the following departments. The below is not a comprehensive list. The most recent validated publications for the school and departments can be seen on their publications pages, linked to from the headings below. Otherwise, read down the entry for recent notifications.

21 Oct 2021

From little things, bigger things grow: ACBD CARE program expands to CCS

The Central Clinical School's CARE schematic

The concept of research and consumer partnerships is not a new one, but the scientific community has increasingly recognised its importance in recent years, with a growing proportion of funding bodies now recommending or requiring consumer engagement for grant pitches. 

The Central Clinical School's Consumer and Researcher Engagement (CCS CARE) program initially developed by researchers and staff within Australian Centre for Blood Diseases (ACBD), is now seeing a growth and roll out at the school-wide level. This growth is remarkable given that the CARE program was only officially launched in February of this year (ccsmonash.blogspot.com/2021/03/launch-of-acbds-community-engagement.html).

20 Oct 2021

Raf Epstein on life in the media machine during the COVID-19 pandemic

Hear from journalist and host of ABC Drive, Raf Epstein, about life in the media machine during the COVID-19 pandemic and his insights into the role of the media during a public health crisis. 

Video: www.youtube.com/watch?v=CGyqoupNWIw

Professor Steve Jane, Dean of the sub-Faculty of Translational Medicine and Public Health at the Alfred Precinct, also announced the winners of the Alfred Research Alliance publication prizes for 2021.

19 Oct 2021

Alfred Research Alliance video showcase 2021

The Alfred Research Alliance precinct is home to more than 1500 researchers and 1100 postgraduate students, all committed to solving some of the biggest health challenges of our time.

To celebrate Alfred Health Week, we asked 20 of them, including CCS's Matt Snelson (Diabetes), Narelle Cox (Respiratory Research@Alfred), Emily Edwards (Immunology and Pathology), Tiffany Phillips (Melbourne Sexual Health Centre), Jason Palazzolo (Australian Centre for Blood Diseases), Julia Sewell (Medical Education) and more to tell us a little bit more about their research, and how it will improve health outcomes for all Australians. Check out their videos!

Video gallery: www.alfredresearchalliance.org.au/research/alfred-health-week-2021/video-showcase-2021/

Imaging of brain tumours (gliomas) research supported by The Aftershock

Prof Meng Law (right) with a colleague. Image: The Aftershock
In 2019, The Aftershock committed to support research within the Department of Neuroscience at Monash University (CCS, Alfred Hospital) led by Professor Meng Law, Dr Jarrel Seah, Dr Andrew Dixon and Dr Jennifer Tang

The research aims to show the potential of using information from MRIs of patients with brain tumours (gliomas) for the prediction of characteristics and future growth with artificial intelligence. The current project aims to collect a large dataset of brain tumours on MRI with associated pathology results, and apply unsupervised deep learning techniques to improve the diagnosis and classification of gliomas and other brain tumours.

See The Aftershock full update.

Looking after your wellbeing and mental health in this pandemic, endemic, and beyond

October is Mental Health Month

By Dr Zhouije Ding and the CCS GEDI committee
 
COVID-19 has significantly changed our daily life, an outcome shared across the world. Here in Melbourne, endless lockdowns and the question of “Will we ever be back to normal?” haunts us all.

When my 6-year old child asked me, “Could we go abroad and visit grandpa and grandma because I miss them so much”, it was definitely a heart-breaking moment, in which all I could think to say was “Yes, we will, one day”.

Petition for NHMRC to create gender equity needs your signature

Female senior academics inequitably receive less funding than males.
Forwarded on behalf of the CCS GEDI committee

A petition has been released calling on medical researchers and the greater scientific community of Australia to challenge the NHMRC to urgently commence at strategic overhaul of current funding schemes to ensure Equitable funding for Women in STEMM.

18 Oct 2021

Participants sought: Treatment for Behavioural Variant Fronto-temporal Dementia (bvFTD)

Imaging of Behavioral Variant Frontotemporal Dementia (bvFTD)
Image:
© Bradford Dickerson
We are seeking participants with behavioural variant Fronto-temporal dementia (bvFTD) for our study.

This research project is looking at whether the trial drug, sodium selenate, decreases the rate of brain shrinkage in patients with bvFTD.

Participants are randomly assigned to one of two groups. One group will receive the study drug, sodium selenate, and the other group will receive a placebo.

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