LIMITS · Lipid Inclusions Modulating Inflammation in Thrombotic Stroke

Each year, 1.1 million inhabitants of Europe suffer stroke. Stroke leads to extensive neuronal loss and results in an environment filled with cellular debris, notably myelin debris. The clearance of this debris by microglia is crucial for restoring homeostasis, but it can overwhelm their phagocytic function. Consequently, damaged areas often exhibit microglia with cytoplasmic inclusions known as lipid droplets (LDs). Recent findings by one of the supervisors indicate that microglia in young mice accumulate LDs, with Plin2 being one of the most differentially expressed genes after brain ischemia.LIMITS aims to characterize the contribution of LDs to the neurological deficits following thrombotic stroke to be exploited as (i) novel markers for monitoring and (ii) novel therapeutic targets. Additionally, we will develop new preclinical models to share with the entire research community.The objectives are: (i) to establish a new strain of transgenic mice with a deletion of the Plin2 gene in microglia, (ii) to characterize the inflammatory response, lesion volume, and neurological function after ischemic stroke of this new strain, and (iii) to identify new pharmacological approaches targeting LDs for the treatment of ischemic stroke. My expertise in inflammation and metabolic reprogramming, the supervisors' established proficiency in clinical and basic stroke research, the lipid expertise of our collaborators, and the availability of all necessary facilities and training opportunities at the host institution will ensure the success of this research.LIMITS project has the potential to uncover innovative therapies for ischemic stroke. Furthermore, since LDs have been shown to play a pivotal role not only in ischemic stroke but also in other conditions such as aging, obesity, and cancer, the results from this project are expected to have a significant impact across various disease areas.