Posted on November 1, 2016

Researchers at Trinity College Dublin will study the interaction between acute illness and brain dysfunction after they were awarded significant funding – a projected $1.2 million over five years — from the US Department of Health and Human Services (DHHS).

Assistant Professor in Neuroscience in the School of Biochemistry and Immunology at Trinity, Colm Cunningham, will use the funding awarded by the National Institute on Aging (NIA) of the US National Institutes of Health to explore why – and how — the brain is sometimes left vulnerable to the negative effects of acute illness.

Although it has not been widely appreciated until recently, acute illness can have negative effects on brain function and can even injure the brain. Delirium is a frequent neuropsychiatric complication of acute illness in the elderly that encompasses profound disorientation and confusion. As well as being extremely distressing and often causing extended stays in hospital, it is now clear that these episodes also accelerate the onset and progression of dementia.

The pathophysiological mechanisms by which acute illness induces cognitive dysfunction and lasting brain injury are poorly understood and this award by the NIH is aimed at unravelling the molecular mechanisms by which inflammation outside the brain alters inflammation inside the brain (neuroinflammation). In particular, the studies will focus on how the loss of a key brain chemical, acetylcholine, whose levels decline with age, alters the activation of brain immune cells called microglia and leaves the brain vulnerable to the negative effects of acute illness.

Professor Cunningham commented: “Evidence that inflammation throughout the body can trigger dysfunction and injury in the brain has been slowly accumulating, but this award allows us to really get into the detail of how the brain becomes vulnerable when acetylcholine levels decline and to examine the role that inflammation plays in disrupting brain performance and integrity. With fantastic tools made by our collaborator John Lowry in Maynooth University, we can also now start to look at how brain metabolism is changing during acute illness.”

Dr Molly Wagster, Chief of NIA’s Behavioral and Systems Neuroscience Branch, said: “We are delighted to support this collaborative investigation into the molecular underpinnings of delirium, a condition once thought transient but that we now know can cause long-term — or even permanent — cognitive problems in older people.”

Although those studies will rely exclusively on mouse models, the group are also pursuing this story in elderly patients who experience acute inflammation in the form of hip fractures, as co-investigators in a collaborative project just funded by Alzheimer’s Research UK. The ASCRIBED study, led by Professor Chris Fox in the University of East Anglia, takes advantage of a cohort of elderly hip-fracture patients from whom brain fluid (CSF) is being collected in order to track the inflammation and brain injury ‘biomarkers’ that are produced as a consequence of the inflammatory trauma of hip fracture.

Professor Cunningham added: “Together, it is hoped that these two studies can begin to piece together how acute inflammation triggers delirium and acute brain injury and to what extent this drives the progression of dementia.”

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