Surprising finding following infection after paediatric brain injury

Mr Rishabh Sharma, first author on the study

Traumatic brain injury (TBI) is a major cause of disability in young children, yet the factors contributing to poor outcomes in this population are not well understood. What most people don’t know is that patients who experience a TBI are highly susceptible to infections originating in hospitals, and are mostly acquired within the first week of hospitalization. Such infections may modify the pathobiology and recovery of TBI.

Mr Rishabh Sharma is a 3rd year PhD student supervised by Dr Bridgette Semple, A/Prof. Sandy Shultz and Dr. Pablo Casillas-Espinosa in the Department of Neuroscience at the Central Clinical School. He wanted to understand whether an additional challenge to the immune system (i.e. mimicking an infection) after paediatric TBI altered the acute outcomes in a pre-clinical mouse model.

In this published study, the research team hypothesised that outcomes would be worsened from a TBI if infection also took place. This would be because an additional infection would prolong the initial inflammatory immune response that occurred from the TBI. They used a toxin from common bacteria - called Lipopolysaccharide - to provide an immune challenge in order to mimic a hospital-acquired infection.

Rishabh Sharma said, “We found that a transient, infection-like systemic challenge did have widespread effects on the brain and immune system, but these were not synergistic with prior TBI in our pediatric mice. That is, it wasn’t like adding fuel to the fire and making it hotter, at least in this model.”

“These findings make a start on understanding the potential influence of a secondary immune challenge to the injured pediatric brain. We need further studies to tease out the chronic effects of this two-hit insult.” 

Ongoing work by Dr Semple’s research group is now examining whether the addition of an infection model early post-injury can affect chronic outcomes, with a particular focus on post-traumatic epilepsy and neurobehavioural co-morbidities.

The study findings were presented at the International Neurotrauma Symposium 2021 recently, where Rishabh Sharma was awarded the University of Adelaide award for best poster presentation (valued at $350).

Read more:

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. https://pubmed.ncbi.nlm.nih.gov/33731173/