Immunometabolic regulation of microglia function in stroke recovery

Stroke is one of the leading causes of death and disability worldwide.

Despite recent improvements in stroke prevention and acute treatment, there is still a very urgent need for promoting stroke recovery to improve patients’ quality of life. Microglia are the predominant brain resident immune cells, in charge of brain homeostasis through immune surveillance.

Emerging evidences suggest that post-stroke microglial reactivity remains incompletely resolved and persists chronically.

ImmunoMet aims to study the impact of persistent inflammatory and dysfunctional traits of microglia during stroke recovery through metabolic reprograming, a set of essential processes key to satisfy the high energetic requirements of immune activation.

To fulfill this goal, ImmunoMet will use novel and cutting-edge methodologies, including sophisticated imaging techniques, multiparametric flow cytometry, metabolomics and single-cell RNA sequencing, to investigate the time course evolution of microglia immunophenotype and the potential shifts in microglial metabolic pathways over the course of stroke.

ImmunoMet will also evaluate the effects of an acute manipulation of microglia cellular metabolism on the stroke recovery, as an approach to tackle chronic neuroinflammation and improve brain functional recovery after stroke.

To this end, ImmunoMet aims to assess microglia immunophenotype in two scenarios: (1) a transgenic mouse line with altered microglia type I IFN signaling, which may regulate energy metabolism, and (2) after administering an itaconate derivate, a modulator of immune cell polarization. ImmunoMet is expected to contribute novel and valuable insights into the immunometabolic adaptations to stroke.

This research will be a crucial for future development of therapies aimed at enhancing the long-term recovery of stroke survivors, addressing a significant socio-healthcare challenge. ImmunoMet will be a major step in my academic career as an international independent researcher.