Abstract

Brain resilience – the ability to maintain or regain function after injury or damage – declines with age, such that older adults often recover more slowly and less completely from strokes and brain injury. It is unclear if this reflects permanent damage or a reversible failure of the brain’s normal repair mechanisms. This project will test the hypothesis that aging keeps support cells called astrocytes in a prolonged inflammatory state after damage, which in turn prevents neural circuits from functionally compensating.

Using a precisely controlled mouse model of brain injury, we will compare behavioral recovery in young and old animals. First, we will map how brain cells change their molecular state over the days and weeks following injury, in order to identify when and how the responses in different ages diverge. Second, we will record the activity of hundreds of neurons during recovery to determine how successful functional compensation emerges, and where it fails with age. Finally, we will causally perturb astrocytes by targeting a key molecular regulator of inflammation. This will test whether persistent inflammatory activation blocks recovery in young brains, and whether reducing it improves recovery in older brains.

This research aims to determine whether aged brains retain a dormant capacity for repair that can be restored. The findings could reveal new strategies for improving recovery after stroke or brain injury and preserving function during aging and neurodegenerative disease.