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Aljabar, P.

Publications and source records attributed to Aljabar, P..

2 recordsLinked to original sources
bioRxiv2024

A spatio-temporaral atlas of the growing brain for fMRI studies

Spatio-temporal atlases of the growing brain can help when building models of brain development, not only for anatomical structure, but also for the changing patterns of activation within the brain. In this paper, we build such an age-dependent atlas using registrations among a large number of anatomical datasets, acquired from neonatal subjects of different ages, and followed by kernel-based regression. fMRI activation data are then registered to this atlas to build a model of the development of brain networks, such as the default and motor networks, at this early age.

neuroscience↗
bioRxiv2018

Loss of the Wnt/β-catenin pathway in microglia of the developing brain drives pro-inflammatory activation leading to white matter injury

Microglia of the developing brain have unique functional properties but how their activation states is regulated is poorly understood. Inflammatory activation of microglia in the still-developing brain of preterm born infants is associated with permanent neurological sequelae in 9 million infants every year. Investigating the regulators of microglial activation in the developing brain with multiple models of neuroinflammation-mediated injury and primary human microglia we found that a reduction in Wnt/{beta}-catenin signalling is necessary and sufficient to drive an oligodendrocyte-injurious microglial phenotype. We validated in a cohort of preterm born infants that genomic variation in the WNT pathway is associated with the levels of connectivity found in their brains. Using a Wnt agonist delivered by a BBB penetrant microglia-specific targeting nanocarrier we prevented in our animal model the pro-inflammatory microglial activation, white matter injury and behavioural deficits. Collectively, these data validate that the Wnt pathway regulates microglial activation, is critical in the evolution of an important form of human brain injury and is a viable therapeutic target.

immunology↗