Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex.

In multiple sclerosis, an inflammatory attack results in myelin loss, which can be partially reversed by remyelination. Recent studies suggest that mature oligodendrocytes could contribute to remyelination by generating new myelin. Here, we show that in a mouse model of cortical multiple sclerosis pathology, surviving oligodendrocytes can indeed extend new proximal processes but rarely generate new myelin internodes. Furthermore, drugs that boost myelin recovery by targeting oligodendrocyte precursor cells did not enhance this alternate mode of myelin regeneration. These data indicate that the contribution of surviving oligodendrocytes to myelin recovery in the inflamed mammalian CNS is minor and inhibited by distinct remyelination brakes.

Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development.

Motile cilia are miniature, propeller-like extensions, emanating from many cell types across the body. Their coordinated beating generates a directional fluid flow, which is essential for various biological processes, from respiration to reproduction. In the nervous system, ependymal cells extend their motile cilia into the brain ventricles and contribute to cerebrospinal fluid (CSF) flow. Although motile cilia are not the only contributors to CSF flow, their functioning is crucial, as patients with motile cilia defects develop clinical features, like hydrocephalus and scoliosis. CSF flow was suggested to primarily deliver nutrients and remove waste, but recent studies emphasized its role in brain development and function. Nevertheless, it remains poorly understood how ciliary beating generates and organizes CSF flow to fulfill these roles. Here, we study motile cilia and CSF flow in the brain ventricles of larval zebrafish. We identified that different populations of motile ciliated cells are spatially organized and generate a directional CSF flow powered by ciliary beating. Our investigations revealed that CSF flow is confined within individual ventricular cavities, with little exchange of fluid between ventricles, despite a pulsatile CSF displacement caused by the heartbeat. Interestingly, our results showed that the ventricular boundaries supporting this compartmentalized CSF flow are abolished during bodily movement, highlighting that multiple physiological processes regulate the hydrodynamics of CSF flow. Finally, we showed that perturbing cilia reduces hydrodynamic coupling between the brain ventricles and disrupts ventricular development. We propose that motile-cilia-generated flow is crucial in regulating the distribution of CSF within and across brain ventricles.