Description

Stroke is a major health concern worldwide, with approximately 25% of people expected to experience one in their lifetime. Current treatments for ischemic stroke, such as thrombolysis and thrombectomy, are effective but not always available for patients, nor do they guarantee complete recovery. This highlights the need of new prognostic and therapeutic tools to improve functional recovery.

Over the past decade, there has been growing interest in studying the link between intestinal immunity and neuroinflammation in stroke. Indeed, alterations in intestinal homeostasis after stroke have been reported in both human and animal studies. However, it is so far not known whether pre-existing intestinal inflammation is a key driver of poor long-term functional recovery post-stroke.

Hence, the objectives of the project are to (i) evaluate how intestinal inflammation influences stroke severity, outcomes, and functional recovery, and (ii) propose innovative therapeutic strategies targeting intestinal inflammation to improve functional recovery after stroke.

To achieve this, the candidate will use a murine model of stroke combined with immuno-MRI targeting specific adhesion molecules. He will also perform flow cytometry and whole-genome sequencing analyses of intestinal intraluminal content to investigate alterations in both intestinal and central immunity, alongside changes in microbiota composition. In addition, post-stroke functional deficits and recovery will be evaluated using functional ultrasound imaging and behavioral tests. Intestinal inflammation and gut microbiota composition will also be evaluated in patients, in relation to neurological deficits and functional recovery. Finally, two innovative therapeutic strategies targeting intestinal inflammation will be tested in mice to improve functional recovery after stroke.