Mar 27, 2024

Inflammation may cause persisting symptoms of traumatic brain injury

Research

By Ben Gane

Up to a third of people who experience a traumatic brain injury (TBI) have persisting symptoms, including headaches, sensitivity to stimuli, and difficulty thinking clearly. Even though as many as 20% of Canadians will experience a TBI in their lifetime, the causes of these persisting symptoms are poorly understood.

Previous research has linked astrogliosis, a type of inflammation that takes place in the brain, to TBIs. Dr. Jeffrey Meyer and his team, including coinvestigators Drs. Isabelle Boileau, Michael Cusimano, Ishrat Husain, and Steve Kish, set out to establish if astrogliosis might continue long after the initial injury and potentially have a role in the persisting symptoms afflicting some patients. Equipped with a promising new chemical imaging agent called C-SL25.1188, their research uncovered evidence of lingering inflammation in the brain – and potential new avenues for treatment.

Dr. Jeffrey Meyer

What is astrogliosis and why is it important to measure it in patients who have experienced traumatic brain injury?

JM: Astrogliosis is an inflammation in the brain that happens in response to traumatic brain injuries. Inflammation is the body's response to infection or trauma, like the redness around a scrape on the skin. Astrogliosis takes place when astrocytes, a type of star-shaped immune cell found in the brain, increase their number or change their shape in response to an injury.

Why is C-SL25.1188 a good tool to use in these measurements?

JM: C-SL25.1188 is an imaging agent. It binds to a protein found in astrocytes. It is an especially useful tool for tracking inflammation because astrocytes make more of the protein C-SL25.1188 binds to when inflammation is taking place.

What motivated this research?

JM: Many people who get a traumatic brain injury have symptoms that persist for years. We haven't developed adequate medication treatments for these symptoms. To create a treatment, we need to know more about the underlying condition. We knew that astrogliosis occurs in animal models of TBI, but we did not know what happens in humans and whether it can last a long time, possibly contributing to symptoms. My hope is that this information can be used to guide the development of therapeutics to cure the long-lasting symptoms of traumatic brain injury.

What was the most important finding of this study, in your opinion?

JM: Astrogliosis can be present in people with persistent, significant symptoms from TBI even years after the last injury occurred.

How does this change treatment in the future?

JM: In the short term, it’s likely that some inflammation in response to an injury is helpful and can be curative. But when such inflammation is present for years, it may contribute to ongoing injury. Suppressing potentially harmful aspects of astrogliosis could be tested in people with chronic traumatic brain injury symptoms.

Any next steps?

JM: I hope to use PET scans to identify TBI cases with high levels of astrogliosis and test out repurposed therapeutics that might lower astrogliosis.

What is the major take home message for the public?

JM: We have shown the first evidence for persistent astrogliosis in people with traumatic brain injury and longstanding symptoms using a specialized brain imaging method. There are likely ways to influence this inflammation to reduce potentially harmful effects and increase potentially helpful effects, some of which we hope to test by repurposing existing medications for other illnesses in the future.

View this month's ImPACT paper.

Koshimori, Y., Cusimano, M. D., Vieira, E. L., Rusjan, P. M., Kish, S. J., Vasdev, N., Moriguchi, S., Boileau, I., Chao, T., Nasser, Z., Husain, M. I., Faiz, K., Braga, J., & Meyer, J. H. (2023). Astrogliosis marker 11C-SL25.1188 PET in traumatic brain injury with persistent symptoms. Brain (London, England : 1878), 146(11), 4469–4475. https://doi.org/10.1093/brain/awad279