Visualizing Clearance of Cerebrospinal Fluid via the Glymphatic System
Evidence strongly suggests that failing drainage of cerebrospinal fluid contributes to neurodegeneration, as the flow of fluid from the brain into the body carries metabolic waste with it. This metabolic waste, such as misfolded amyloid-β, becomes more prone to accumulate given the reduced drainage that occurs in later life, and this accumulation contributes to the onset and progression of neurodegenerative conditions. One of the pathways for drainage is the comparatively recently discovered glymphatic system. Here, researchers discuss a way to measure the flow of cerebrospinal fluid through the glymphatic system. Putting numbers to the problem of reduced drainage is an important step on the way to doing something about it.
Glymphatic clearance dysfunction may play an important role in a variety of neurodegenerative diseases and the progression of ageing. However, in vivo imaging of the glymphatic system is challenging. In this study, we describe an MRI method based on chemical exchange saturation transfer (CEST) of the Angiopep-2 probe to visualize the clearance function of the glymphatic system.
We injected rats with Angiopep-2 via the tail vein and performed in vivo MRI at 7 T to track differences in Angiopep-2 signal changes; we then applied the same principles in a bilateral deep cervical lymph node ligation rat model and in ageing rats. We demonstrated the feasibility of Angiopep-2 CEST for visualizing the clearance function of the glymphatic system. Finally, a pathological assessment was performed. Within the model group, the deep cervical lymph node ligation group and the ageing group showed higher CEST signal than the control group. We conclude that this new MRI method can visualize clearance in the glymphatic system.