A method for detecting molecular transport within the cerebral ventricles of live zebrafish (Danio rerio) larvae

The production and flow of cerebrospinal fluid performs an important role in the development and homeostasis of the central nervous system. However, these processes are difficult to study in the mammalian brain because the ventricles are situated deep within the parenchyma. In this communication we introduce the zebrafish larva as an in vivo model for studying cerebral ventricle and blood-brain barrier function. Using confocal microscopy we show that zebrafish ventricles are topologically similar to those of the mammalian brain. We describe a new method for measuring the dynamics of molecular transport within the ventricles of live zebrafish by means of the uncaging of a fluorescein derivative. Furthermore, we determine that in 5-6 days post-fertilization zebrafish, the dispersal of molecules in the ventricles is driven by a combination of ciliary motion and diffusion. The zebrafish presents a tractable system with the advantage of genetics, size and transparency for exploring ventricular physiology and for mounting large-scale high throughput experiments