Targeting neuroinflammation to limit neuronal cell damage in traumatic brain injury

Traumatic brain injury (TBI) remains the leading cause of death and permanent disability in adolescents worldwide.

More than 50 million people worldwide have a TBI each year, and it is estimated that about half the world’s population will have one or more TBIs over their lifetime. TBI has been estimated to cost the global economy approximately billion annually. Despite the improvement of neurosurgical procedures as well as critical care management, morbidity and mortality are still high and approximately 25% of these patients remain with permanent disabilities becoming a familiar, social and economic burden for society. A better understanding of events occurring in the brain after traumatic brain injury is essential to identify ways to limit the damage and ultimately improve the outcome. There are no viable treatments available to a clinician when caring for a patient after a TBI. It is clear that current thinking and programs have failed. Over the past decade, it has become clear that neuroinflammation is central to the brain’s response to trauma. TBI triggers acute neuroinflammation, which exacerbates the primary brain damage. In addition, cognitive deficits that follow TBI have been linked to neuroinflammation, suggesting that targeting this response may be beneficial in limiting both the acute and long-term damaging effects to the brain.

The overall aim of this proposal is to characterise the early neuroinflammatory events that are associated with alterations in neuronal populations and cognitive decline following traumatic brain injury. Specifically, this project will focus on the role that the type-I interferons play in modulating neuroinflammation by utilising state of the art genetic knock-out models and clinically relevant therapeutics to influence TBI outcome. The data generated by this project will not only be used to further understand the molecular pathways that are changed in the brain after TBI but to develop novel therapeutics to reduce the long-term debilitating effects of TBI.

These findings will significantly benefit TBI research but will also be of future interest to research into neurodegenerative diseases where chronic inflammation in the brain has long been suggested to contribute to neuronal cell death. By defining the neuroinflammatory and immunoregulatory processes, we will aid the development of anti-neuroinflammatory approaches that delay the onset or slow the progression of neural cell death and brain dysfunction following TBI.

Supervision team

The University of Melbourne:

• Dr Juliet Taylor
• Professor Peter Crack

The University of Manchester:

• Professor Michael Harte
• Professor Stuart Allan
• Dr Andrew Greenhalgh

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Further details