Re-orchestrating Neuroimmunity After Stroke to Improve Long-Term Recovery

Stroke is a leading cause of long-term disability worldwide. While immediate medical care for ischemic stroke has improved, many survivors continue to suffer from persistent symptoms such as post-stroke depression (PSD), post-stroke fatigue (PSF), and cognitive decline, which can last for months or even years. These chronic effects are poorly understood and currently lack effective treatment. Recent evidence suggests that abnormal or prolonged immune responses in the brain may contribute significantly to these long-term issues.
This project aims to investigate how the brain’s immune system, particularly the interaction between T lymphocytes and microglia (the brain’s resident immune cells), influences both damage and recovery after stroke. Special attention is given to white matter (WM) and axonal damage, which disrupts communication between different brain regions and is closely linked to cognitive and emotional problems.
Using a clinically relevant experimental model of ischemic stroke, we will combine behavioral testing (to assess memory, mood, and fatigue) with advanced imaging techniques such as longitudinal MRI to monitor changes in brain structure, white matter integrity, and blood-brain barrier function over time. The study will also explore the role of immune cell activity in white matter areas far from the initial stroke site.
Importantly, the project will evaluate whether modulating a specific type of immune cell—regulatory T cells (Tregs)—can reduce inflammation, prevent further neural damage, and support brain repair. By focusing on the immune system’s role in the delayed phases of stroke, this research could open the door to innovative treatments targeting the long-term consequences of stroke, which are a major unmet medical need.