Characterization of tertiary neurodegenerative lesions in Encephalopathy of Prematurity – PremAging

Encephalopathy of prematurity (EoP) includes all brain lesions linked to prematurity. EoP is responsible for cellular events leading to permanent motor and/or cognitive deficits. The main risk factor for EoP is infections in the perinatal period. The microglia, a resident macrophage of the central nervous system, is the conductor of the brain through a complex dialogue with other brain cells. In an inflammatory context, the microglia activate and release pro-inflammatory molecules leading to neuroinflammation. Some pathological mechanisms of EoP are like those observed in certain brain pathologies such as autism spectrum disorders and neurodegenerative diseases. Studies show that one of the pivotal phenomena of aging is neuroinflammation. Our hypothesis is that the priming of microglia during development could promote the onset of early aging. The originality of this project will be to analyze how the brain disruption induced by EoP can have long-term neuronal consequences. In a model of perinatal inflammation by injection of the pro-inflammatory cytokine IL-1beta, we will study the consequences during the tertiary phase of EoP. More specifically, we wish to assess several months after the acute phase (i) the presence of chronic neuroinflammation, (ii) associated neuronal involvement and (iii) deficits in brain connectivity and behavior that could suggest premature aging. This study would make it possible to assess prematurity as a new risk factor for the development of aging in humans and therefore improve patient care. In addition, the precise analysis of the cellular mechanisms involved in this early aging will allow the identification of new therapeutic targets.