Antibody treatment helps preventing long-term effects of traumatic brain injury: Gladstone Institute study

September 12, 2021 0 By Zahra Ahmed

Researchers have identified a specific molecule in a part of the brain called the thalamus that plays a key role in secondary effects of traumatic brain injury, such as sleep disruption, epileptic activity, and inflammation. The new study, which was published in the journal Science, also found that an antibody treatment could prevent the development of these negative outcomes. 

“No therapies currently exist to prevent the disabilities that can develop after a brain trauma,” said Jeanne Paz, PhD, associate investigator at Gladstone Institutes. “So, understanding how the traumatic brain injury affects the brain, especially in the long term, is a really important gap in research that could help develop new and better treatment options.”

 Paz and her team recorded the activity of different cells and circuits in the brain of mice after brain injury. They found that a molecule called C1q was present at abnormally high levels in the thalamus for months after the initial injury, and these high levels were associated with inflammation, dysfunctional brain circuits, and the death of neurons.

The Institute collaborated with Eleonora Aronica, MD, PhD, a neuropathologist at the University of Amsterdam, to validate their findings in human brain tissues obtained from autopsies.  

They found high levels of the C1q molecule in the thalamus 8 days after people had sustained a traumatic brain injury. 

“Our study answered some very big questions in the field about where and how changes are happening in the brain after a trauma, and which ones are actually important for causing deficits,” said Paz.

The C1q molecule plays an important role in brain development.”C1q can be both good and bad,” said  Paz. “We wanted to find a way to prevent this molecule’s detrimental effect, but without impacting its beneficial role.”

When the researchers studied mice genetically engineered to lack C1q at the time of the trauma, the brain injury appeared much worse. However, when they selectively blocked C1q with the antibody during the latent phase, they prevented chronic inflammation and the loss of neurons in the thalamus.

“This indicates that the C1q molecule shouldn’t be blocked at the time of injury, because it’s likely very important at this stage for protecting the brain and helping prevent cell death,” said Holden. “But at later time points, blocking C1q can actually reduce harmful inflammatory responses.”