Brain’s immune cells respond differently to injury depending on age

Microglia, the brain’s resident immune cells, play a vital role in protecting the central nervous system by fighting infections and clearing harmful agents. But how do these cells behave throughout life — from birth to old age — and how do they react to different types of brain injury over time? These are the questions a team of international researchers, led by Vanessa Coelho-Santos from the University of Coimbra (UC), set out to answer.

Their findings reveal that microglia change significantly with age and respond differently to brain injuries depending on the life stage. The research may pave the way for age-specific and injury-specific therapeutic strategies.

“In this study, we used a high-precision laser to create targeted brain tissue damage and, with the same intensity, simulate vascular injuries that temporarily block blood flow,” explains Vanessa Coelho-Santos. “This allowed us to compare microglial responses to different types of injury across the lifespan. We found that age has a marked effect on the morphology and behaviour of these cells in response to injury.”

According to the researcher from UC’s Centre for Biomedical Imaging and Translational Research (CIBIT) at the Institute for Nuclear Sciences Applied to Health (ICNAS), these differences may help explain why the brain is more vulnerable to certain conditions at different life stages. “For example, inflammatory responses early in life may be linked to neurodevelopmental disorders, while in later life, weakened microglial responses might contribute to poor recovery after injury,” she adds.

Despite their critical role in brain function, much remains unknown about how microglia evolve throughout our lives. To address this, Coelho-Santos and her colleagues at the Seattle Children’s Research Institute studied the morphological and functional changes in microglia from birth through old age. They also examined how these cells respond to two types of localised brain injury across different ages — an area that had received little attention until now.