Loss of AQP4 impairs solute clearance from the CSF space

Motivation: Aquaporin-4 (AQP4) water channels are thought to play an important role in cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange. However, the effect of AQP4 on CSF drainage and dynamics has not been well-established. Goal(s): To investigate the effects of AQP4 on CSF drainage and dynamics using in vivo imaging. Approach: We performed a whole-brain analysis including CSF spaces and drainage pathways of AQP4 knockout rats using dynamic contrast-enhanced (DCE) MRI with intrathecal gadolinium-based contrast agent administration. Results: DCE-MRI showed that loss of AQP4 impairs solute clearance from the CSF space and reduces CSF-ISF exchange. Impact: Loss of AQP4 impairs CSF-ISF exchange as well as solute clearance from the CSF space, suggesting that AQP4 expression might affect the entire CSF dynamics.