Analysis of cerebrospinal fluid flow in hydrocephalic mouse models of primary ciliary dyskinesia (1125.1)

Abstract

Patients with primary ciliary dyskinesia (PCD) suffer from a variety of disorders that include chronic sinusitis, otitis media, infertility, situs inversus, and hydrocephalus. We have shown that two mouse models of PCD, nm1054 and bgh, have hydrocephalus characterized by dilatation of the lateral ventricles. These models also have male infertility and sinus abnormalities that result from a decrease in respiratory ciliary beat frequency. We therefore hypothesize that the hydrocephalus results from dysfunction of ependymal cilia that prevents proper cerebrospinal fluid (CSF) flow. To investigate CSF flow in vivo, we injected India ink into the lateral ventricles of live mice and histologically demonstrated that ink migrated through the ventricular system of wild type mice but failed to progress past the cerebral aqueduct of either mutant. To validate that this defect was directly due to ciliary dysfunction, we used an ex vivo method to measure ink flow rate over the ependymal cells on dissected ventricular walls. This method demonstrated a decreased flow rate and altered directional flow in the mutant brains, confirming that ependymal ciliary function is required for proper CSF flow. Grant Funding Source: Supported by the NIH NIGMS (1P20GM103620‐01A1) and an NSF REU (1262744)