Neuroprotective functions of the blood-CSF-brain interfaces

The brain is protected from mechanical stress by the circulating cerebrospinal fluid, which also has a key role in brain signalling, neuroimmune surveillance, nutrient supply and in providing buffering capacity for extracellular fluids. Choroid plexuses located at the roof of all four brain ventricles are responsible for CSF secretion and they form a unique interface between two circulating fluids, blood and cerebrospinal fluid. The ependyma lining the ventricles forms an interface and a site of exchange between the CSF and the brain tissue. Although the interfaces formed by Choroid plexus and ependyma are crucial for neuroprotection and affect the bioavailability of many drugs, they have not been much studied. Available evidence suggests that the nature and/or level of expression of transporters and enzymes in choroid plexuses and ependyma are different from those of the intensively studied blood-brain barrier. This post doc study aims to a detailed characterization of the neuroprotective functions of choroid plexus and ependyma. The study focuses on relative expression, functional characteristics and transport directionality of the multispecific transporters located in these interfaces. We aim to clarify whether the transporters and metabolic enzymes form a unique neuroprotective barrier in the choroid plexus or in the ependyma. The results would help in understanding the mechanisms responsible for maintaining the cellular and molecular homeostasis of the CNS, and also in understanding the neuropathological states such as inflammatory and degenerative diseases. Better knowledge of protective mechanisms at brain interfaces would help in drug design, and targeted drug delivery into the CNS.