FLUID

Fluids and Barriers of the Central Nervous System
Objectives

The CNS is separated from the blood by different cellular interfaces.

Our project aims at identifying in each of these interfaces, the various mechanisms which protect the CNS, especially the vulnerable maturing brain during development, It also seeks to explore therapeutic strategies to restore CNS barrier functions challenged by perinatal insults and prevent associated neurological diseases and their long-term sequelae.

Methods and Techniques

The team has developed in vitro models of brain interfaces to study cell trafficking and molecule transfer, as well as in vivo techniques to measure blood-CSF and blood-brain permeability in new-born rodents. Pathophysiological and pharmacological investigations are performed in animal models of perinatal diseases including genetically modified animals, using small animal imaging, molecular and biochemical approaches, analytical chemistry and state-of-the art cellular imaging. Findings are confronted to human brain imaging data in paediatric patients.

Research Project

The efficacy of the blood-brain interfaces and the cerebrospinal fluid in protecting the CNS from noxious compounds and pathogens, maintaining cerebral homeostasis, and controlling neuro-immune interactions is crucial for normal brain function. The perinatal and early postnatal ages are critical periods for brain development and maturation.

Our team explores:

1/ unforeseen detoxifying metabolic and transport processes by which the blood-brain barrier, the blood-CSF barrier, and the ependyma protect the developing brain, as this knowledge is needed to rationalize drug delivery to the pediatric brain,

2/ the deregulation of neuroprotective and neuroimmune functions of blood-brain interfaces in perinatal toxicology and diseases, including jaundice, hypoxia, infection, and intrauterine growth restriction, and

3/ new valuable therapeutic manipulations to restore deficient barrier protection in neonates and to control blood-CSF immune cell trafficking occurring during perinatal injuries.

The new methods and models that are being developed to implement our research activities are  also valorized for external collaborative studies in the brain barrier field through the BIP facility (Blood-brain Interface exploratory Platform, IHU-CESAME, PIA, “Investment for the Future Program”)