Description du projet
Interactions neurovasculaires chez les nouveau-nés
Le cerveau régule sa propre circulation sanguine pour répondre aux fortes demandes métaboliques et énergétiques grâce à un mécanisme appelé «couplage neurovasculaire». La technique BOLD (dépendant de la concentration sanguine en oxygène) est une méthode non invasive qui permet de mesurer l’activité cérébrale en quantifiant les changements au niveau de l’oxygénation des tissus et de la circulation sanguine. Des études menées chez les nouveau-nés utilisant la méthode BOLD indiquent une variation inexpliquée, qui permettrait de mieux comprendre le développement et l’hémodynamique du cerveau. Le projet 2BOLD, financé par l’UE, a pour ambition de mettre au jour les changements spatio-temporels au niveau de l’hémodynamique au cours du développement du cerveau afin de comprendre le couplage neurovasculaire. En utilisant un modèle murin, les chercheurs combineront les données hémodynamiques et vasculaires avec les mesures de l’activité métabolique pour élucider ce mécanisme.
Objectif
Blood oxygen level-dependent (BOLD) functional brain imaging is a valuable non-invasive tool widely used in studies of brain development in health and disease, which relies on blood flow and oxygenation state to provide insights into brain function. Intriguingly, functional imaging studies in the newborn developing brain often report unexplained variation and early inverted hemodynamic responses. There is a gap in knowledge to explain the discrepancy in the newborn hemodynamic signals that needs to be addressed for a better understanding of functional imaging data. The main goal of this project is to identify the origins of this shift. This will be achieved through the combination of a multidisciplinary team with cutting-edge methodologies to study the neonatal brain development in the living mouse. 2BOLD will implement specific aims that leverage innovative non-invasive imaging with a mechanistic insight approach. In Aim 1, we will longitudinally track, using suited pre-clinical imaging, the co-development of hemodynamic, vascular, and metabolic activity. Here, we aim to resolve the spatiotemporal developmental switch from negative to positive responses. In Aim 2, we will use in vivo 2-photon microscopy, novel transgenic animals and optogenetic manipulation to elucidate if the emergence of perivascular astrocytic endfeet is linked with cerebrovascular tone development and neurovascular coupling. Lastly, in Aim 3, live imaging will be complemented by comprehensive proteomic and metabolomic profiling of cerebrovascular maturation associated with the hemodynamic changes. This groundbreaking project will capture the dynamics of cerebrovascular events and hemodynamic signatures with unprecedented detail in the intact mammalian neonatal brain. This advance may pave the way for mechanistic studies on how injury or other adverse processes might derail normal development, with an impact on the diagnosis and treatment of neonatal brain pathologies, such as cerebral palsy.
Champ scientifique
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Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
3004-531 Coimbra
Portugal