31 Jan 2019

Study sheds light on reason why children fare worse after brain injury

by Anne Crawford

Dr Bridgette Semple (standing) and Research Assistant
Larissa Dill
Growing research suggests that children may be more vulnerable to developing long-term cognitive and social behaviour problems after traumatic brain injury (TBI) compared to adults but the reasons why are unclear.

A study by Department of Neuroscience scientist Dr Bridgette Semple and colleagues has probed this under-researched area and points to biological mechanisms that might be responsible. The study, published in the Journal of Comparative Neurology, also suggests a potential treatment strategy.

TBI is the leading cause of mortality and morbidity in young children, 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 inflammation contributes to that progressive damage,” she said.

TBI in children is now treated in essentially the same way as adults through medical management trying to 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’s laboratory conducted experiments in mice with TBI the equivalent age of toddlers compared to adult mice and found elevated levels of a protein called high-mobility group box protein 1 (HMGB1) in the blood of paediatric TBI mice, which were not evident in adult serum.

HMGB1 is released by immune cells when they are damaged or activated and triggers inflammatory processes early on.

“We confirmed previous studies that have demonstrated the inflammatory response is influenced by age-at-insult but identifying HMGB1 in the paediatric brain is very novel,” Dr Semple said.

“The study really suggested to us that HMGB1 could be a target for treatment in the future,” she said. “The idea is that if we could give a drug treatment to patients in the early days after their injury that would stop or reduce inflammatory responses and improve long-term outcomes,” she said.

The Monash researchers have been testing a naturally occurring compound that blocks HMGB1 with results on that research yet to be published.

First author was Dr Kyria Webster, then a PhD student at the University of Melbourne, now a Technical Sales Specialist at Genesearch.

Webster KM, Sun M, Crack PJ, O'Brien TJ, Shultz SR, Semple BD. Age-dependent release of high-mobility group box protein-1 (HMGB1) and cellular neuroinflammation after traumatic brain injury in mice. J Comp Neurol. 2018 Nov 30. doi: 10.1002/cne.24589. [Epub ahead of print]

See more of Dr Semple's work at monash.edu/medicine/ccs/neuroscience/research/semple-group

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