CORDIS - EU research results
CORDIS

Deciphering the neonatal shift in neurovascular coupling: a multimodal approach

Project description

Neuronal-vascular association in neonates

The brain regulates its own blood flow to meet the high metabolic and energy demands through a mechanism known as neurovascular coupling. Blood oxygenation level-dependent (BOLD) technique is a non-invasive method used to measure brain activity by quantifying the changes in tissue oxygenation and blood flow. Studies in newborns using BOLD indicate an unexplained variation, potentially offering an avenue for better understanding of brain development and haemodynamics. The EU-funded 2BOLD project aims to resolve spatiotemporal changes in haemodynamics during brain development to understand neurovascular coupling. Using a mouse model, researchers will combine haemodynamic and vascular data alongside metabolic activity measurements to decipher the mechanism.

Objective

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.

Coordinator

UNIVERSIDADE DE COIMBRA
Net EU contribution
€ 172 618,56
Address
PACO DAS ESCOLAS
3004-531 Coimbra
Portugal

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Region
Continente Centro (PT) Região de Coimbra
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data