Intestinal MAdCAM-1 assessment for prognostic and improvement of functional outcome in stroke.

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.

The INSERM unit “Physiopathology and Imaging of Neurological Disorders – PhIND”, headed by Prof. Denis Vivien, is internationally recognized for its expertise in stroke research and imaging innovation.

The unit is based at the Cyceron center in Caen (Normandie, France), a leading research facility dedicated to in vivo imaging and part of the France Life Imaging network. This environment provides access to a broad range of advanced imaging technologies for preclinical research, including 7T MRI  and PET systems for small animals, magnetic particle imaging (MPI), intravital two-photon microscopy, and photoacoustic imaging. In addition, the center offers core facilities in molecular and cellular biology, experimental surgery, and in vivo experimentation, as well as a large animal facility affiliated with the University of Caen-Normandie.

The team also benefits from its own advanced equipment, including state-of-the-art microscopy systems such as confocal and STED microscopy, calcium imaging, spinning-disc epifluorescence microscopy, along with dedicated analysis tools. Additional techniques available within the group include Doppler speckle imaging, fast ultrasound imaging, and behavioral testing platforms.

Furthermore, the unit is affiliated with the Blood, Brain and Memory @ Caen-Normandie (BBM@C) institute, which hosts several technological platforms dedicated to sequencing (InnovaSeq), the storage and analysis of human samples (InnovaBIO), and advanced microscopy (France Bio Imaging network), providing facilitated access to these resources.

The candidate must hold a Master’s degree in neuroscience, neurobiology, or biology. They must also possess the French regulatory certifications related to animal experimentation or an equivalent qualification (e.g., FELASA accreditation). The candidate should demonstrate a strong interest in preclinical research (animal models of stroke), translational research, as well as in the connections between the gut and the central nervous system and holistic approaches in neuroscience. The candidate must be proficient in either French or English. Prior experience with the techniques used in this project (small-animal MRI, flow cytometry, genomic analyses, etc.) will be appreciated.