Inflamed Astrocytes May Lead to Glioma Formation

A recent study led by the UCL Cancer Institute has shed new light on how injury could contribute to the development of glioma, a rare and aggressive brain tumor. While previous studies have hinted at a possible link between head injury and increased rates of brain tumors, the evidence has been inconclusive. Now, researchers at UCL have identified a possible mechanism that links genetic mutations, brain inflammation and changes in cell behavior.

In their study, published in the journal Current Biology, the team worked with pre-clinical mouse models and found that cell behavior changed when injury caused mutations to act in tandem with brain tissue inflammation. Ultimately, these alterations were found to make them more likely to become cancerous. They also noted that astrocytes, a type of brain cell, can exhibit stem cell behavior after injury, potentially leading to tumors. 

Lead author Professor Simona Parrinello, Head of the Samantha Dickson Brain Cancer Unit and co-lead of the Cancer Research UK Brain Tumour Centre of Excellence, says, “We know that normal tissues carry many mutations which seem to just sit there and not have any major effects. Our findings suggest that if on top of those mutations, an injury occurs, it creates a synergistic effect. In a young brain, basal inflammation is low so the mutations seem to be kept in check even after a serious brain injury. However, upon aging, our mouse work suggests that inflammation increases throughout the brain but more intensely at the site of the earlier injury. This may reach a certain threshold after which the mutation now begins to manifest itself.”

The mice were allowed to age and the cells were studied again, showing that they had reverted entirely to a stem-like state, indicating early glioma cells that could divide. The researchers also showed that inflammation caused by a solution injected into mice accelerated cellular alterations.

The UCL team also worked with Dr. Alvina Lai in UCL’s Institute of Health Informatics to look for evidence to support their hypothesis in human populations. They consulted the electronic medical records of over 20,000 people diagnosed with head injuries, comparing the rate of brain cancer with a control group matched for age, sex and socioeconomic status.

They found that patients who had experienced a head injury were nearly four times more likely to develop a form of brain cancer later in life than those with no head injury. However, the study’s authors noted that the risk of developing brain cancer is overall low, estimated at less than 1% over a lifetime and that the risk remains modest even after an injury.

This study has highlighted the importance of exploring the relevance of the findings in human gliomas. The UCL team’s research suggests that further investigations could help identify ways to prevent brain tumor formation following a head injury.

The team’s study could also affect how injuries are managed in sports such as football and rugby, where the risk of head injury is high. The study’s authors pointed out that it may be possible to develop drugs to protect against the formation of brain tumors following a head injury. Although these findings are still the early stages, it provides an essential insight into the molecular mechanisms behind glioma formation, which could lead to better future prevention and treatment of the condition.