Re-orchestrating neuroimmunity after stroke to improve long-term recovery

Re-orchestrating neuroimmunity after stroke
to improve long-term recovery
Principal investigator: Marina Rubio
Marina Rubio
Stroke, particularly ischemic stroke (IS), is a leading cause of disability and death, resulting in
long-term behavioral deficits due to brain cell damage and death. While most research has
focused on the early stages of IS, it is increasingly recognized as a long-term condition, with
survivors often suffering from cognitive impairments, post-stroke depression (PSD), and
fatigue (PSF). These chronic symptoms significantly impact patients’ autonomy, yet effective
treatments for the long-term effects of IS are lacking.
Our project aims to explore the under-researched area of white matter (WM) damage
following IS, which not only disrupts communication between brain regions but also causes
remote grey matter dysfunction, leading to cognitive and motor impairments. Our working
hypothesis is that the T cell/microglial crosstalk could be a key step in the long-term
modulation of the immune reactions to stroke and to stroke recovery, on a process whose
final goal would be the resolution of inflammation and eventual synaptic remodelling and
remyelination. This project will allow the in-deep understanding of the neuroimmune
processes orchestrating delayed axonal and neuronal degeneration and subsequent
regeneration after stroke that could be responsible for the long-term silent sequelae of stroke.
This research is novel in its focus on long-term neuroimmune responses, the inclusion of WM
regions beyond the ischemic core, and the use of a clinically relevant experimental stroke
model. The potential therapeutic strategy of targeting Treg-microglia communication could
offer new avenues for treating the chronic consequences of ischemic stroke.