Organoïdes cérébraux humains et barrières cérébrales pour l'étude de lésions hypoxiques cérébrales : découverte de biomarqueurs

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neurological disorders during the newborns period. This brain disease is multifactorial with a huge global impact, and a lack of effective treatments making it a critical medical challenge. This project focuses on the development of human 3D translational models, including cerebral organoids and brain barriers derived from induced pluripotent stem cells, in order to mimic neonatal hypoxic conditions. Choroid plexus organoids which secrete cerebrospinal fluid (CSF)-like fluid in vitro and blood-brain barrier (BBB) in vitro were established to model hypoxic pathophysiology. Hypoxia disrupted theintegrity of brain barriers, with an increase of BBB permeability and impaired neurogenic signalling in CSF-like fluid secreted from choroid plexus organoids. Comparative proteomic analysis between healthy and hypoxic choroid plexus organoids revealed important alterations related to neurogenesis, energy metabolism, and mitochondrial function. Meaningful sex-specific differences were observed in cerebral organoids, particularly in CCT chaperone proteins and metabolic pathways. These innovative translational models enable the identification of novel biomarkers and the evaluation of promising neuroprotective strategies.