Breakthrough in treatment for brain trauma

L-R: Maria Daglas (first author), Maithili Sashindranath, Rob Medcalf

Monash University scientists have made a major breakthrough in understanding how our immune system response to head trauma leads to ongoing, long-term health problems.

A study by Australian Centre for Blood Diseases (ACBD) researchers finds an increase in immune cells in the brain following head trauma. These cells, when over-activated, contribute to deterioration in brain function over time. The findings open the door to potential developments for drugs to prevent long-term brain damage.

Professor Robert Medcalf and his group discovered that, in the months following head trauma, there is a persistent increase in the levels of immune cells, known as CD8 T cells. Their overactivity contributes to deterioration in brain function, particularly affecting motor function.

When these immune cells are removed or prevented from accumulating, the brain remains capable and healthy.

The discovery, published in the journal Cell Reports, has now opened the door to potential developments for drugs to prevent long-term brain damage.

“Right now, there’s no specific drug treatment for head trauma,” said Professor Medcalf, head of ACBD's Laboratory of Molecular Neurotrauma and Haemostasis. “If anyone has a brain trauma, they’re at risk of long-term disability."

Co-senior author Dr Maithili Sashindranath, also in ACBD, said traumatic brain injury could lead to long-term movement and gait disturbances.

She said, “It now appears that the persistently activated adaptive immune system has a direct role in this.

“This finding suggests that it might be possible to use therapies that block entry of T-cells (specifically CD8 T cells) into the brain to minimise the risk of long-term disability after brain trauma.”

The researchers used two methods to study the role of CD8 T cells in brain trauma. They genetically removed the CD8 T cells from the mice before injury, and also tested an antibody to deplete these cells.

Both strategies improved movement and gait disturbances in these mice.

“The implication is that this provides an opportunity to develop a drug treatment to prevent long-term brain damage.”

Professor Medcalf congratulated the research team, particularly the first author, Dr Maria Daglas, who undertook the study as part of her PhD.

Reference
Daglas, M, Draxler, D.F., Ho, H., McCutcheon, F., Galle, A, Au, A-E, Larsson, P., Gregory, J., Alderuccio, F., Sashindranath, M and Medcalf, R.L. (2018). Activated CD8+ T cells cause long-term neurological dysfunction following traumatic brain injury. Cell Reports, in press Oct 2019