The network of cilia-driven flows: the silent provider of the brain’s logistic needs with spatiotemporal sensitivity
The brain is immersed in cerebrospinal fluid (CSF), a clear liquid that is constantly secreted from choroid plexus into the ventricular system and flows in caudal direction until reaching the subarachnoid space where it circulates around the brain and finally is reabsorbed. A variety of functions are attributed to this unidirectional flow including delivery of nutrients, clearance of toxic metabolites, and formation of chemokine gradients during brain development. Regarding the wider range of CSF-components and the broad fluid-dynamics, it remains unclear how the comparably huge volume of the CSF-filled ventricular system might possibly home distinguished and even opposing functions.
We discovered that cilia-generated flow along the ependymal lining of the ventricular system forms a mosaic-like-pattern and subdivides CSF into small volumes allowing for regional abundance of CSF-components. In certain areas, the cilia-generated flow forms complex channel-like networks that might spatially separate clearance of toxins from precise, timely, and efficient transport of neurosecretions between distant brain areas. In contrast to cellular connections, such flow-channel connections dissolve easily and change direction in response to physiological, environmental, and behavioral cues mediated by a minor change of cilia beating direction on the surface of few ependymal cells. We identified genes that are associated with both, change in the pattern of this network in mice and also debilitating disease in humans.
These findings support our hypothesis that the impact of CSF-flow exceeds the function of embedding the brain in a nourishing and protective milieu. Our current and future work will identify processes in the brain that rely on these transport logistics. We address developmental, behavioral and physiologic consequences of dislocated or interrupted connections. Identification of environmental and endogenous factors that affect of the networking of the channels promote understanding of disease mechanisms and potential treatment.