The choroid plexus maintains ventricle volume and adult subventricular zone neuroblast pool, which facilitates post-stroke neurogenesis

Abstract

The brain's neuroreparative capacity after injuries such as ischemic stroke is contained in the brain's neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here we report a mouse genetic tool (the ROSA26iDTR mouse line) for non-invasive, specific, and temporally controllable ablation of CSF-producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at one-month post-ablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the MCAo model of ischemic stroke, neuroblast migration into the lesion site was also reduced in the CSF-depleted mice. Thus, our study establishes an important and novel role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke.