The Embryonic Blood-CSF Barrier Has Molecular Elements to Control E-CSF Osmolarity During Early CNS Development

In vertebrates, brain development takes place at the expanded anterior end of the neural tube. After closure of the anterior neuropore, the brain wall forms a physiologically sealed cavity that encloses embryonic cerebrospinal fluid (E-CSF), a complex and protein-rich fluid. E-CSF has several crucial roles in brain anlagen development. In this respect, during the initiation of neurogenesis, increases in the volume of brain cavities account for 70% of the total growth of the brain primordium, and are accompanied by a parallel increase in E-CSF volume. Recently, we reported the presence of several blood vessels located in the brain stem lateral to the ventral midline, at the mesencephalon and prosencephalon level, which have a transient blood-CSF barrier function in chick embryos by transporting proteins in a selective manner via transcellular routes. These blood vessels control E-CSF protein composition and homeostasis during this early stage of CNS development, just after closure of the neuropores. Here we report that in chick and rat embryos these same blood vessels, which lie close to the neuroectoderm, express several molecules related to water and ion transport, namely AQP1, AQP4 and Kir4.1. Our results confirm that a blood-CSF barrier controls E-CSF composition and homeostasis from early stages of brain development in chick embryos, including water and ion influx, thus regulating E-CSF osmolarity. On the basis of our findings, we also propose that a similar blood-CSF barrier is present in mammals at equivalent developmental stages of the brain.