Our trainees review webinars in their given fields and share abstracts to help colleagues outside their discipline make an informed choice about watching them. As our program bridges diverse disciplines, these abstracts are beneficial for our own group in helping one another gain key knowledge in each other’s fields. We are happy to share these here for anyone else who may find them helpful.
Douglas H. Kelly, PhD
Bobby Jones Chiari & Syringomyelia Foundation
Cerebral spinal fluid (CSF) flows in perivascular spaces (PVSs) (spaces around the vasculature) and plays a role in clearing the brain of metabolic waste. If the waste is not cleared efficiently it can result in brain damage and Alzheimer’s Disease. To study how CSF flows, dye can be injected into the cisterna magna (CSF space) of live mice and imaged to see how the CSF moves within the PVS. Gadolinium tracer can also be injected into humans and its flow can be imaged using MRI. With mice, a cranial window can be implanted so the brain is visible from the outside. The CSF flows from outside the brain into the PVS, which is called CSF influx. Microsphere’s injected into the mice become visible through the cranial window, making it possible to study the flow of CSF within the PVSs.
The CSF in the PVS flows in the same direction as the blood. When the flow velocity is plotted over time, it shows the velocity is fast at narrow spaces and slower at bifurcations, when PVSs branch from going one direction to two. The flow has a Reynolds number that is low, indicating laminar flow. This flow is important because amyloid beta (a commonly studied metabolic waste thought to contribute to Alzheimer’s) move more by fluid flow than by diffusion.
To find out what causes the CSF to pulse, heartbeats and respiration were correlated with the CSF flow velocity within the PVS. The heartbeat was correlated more with the pulsation of the CSF than respiration, so pulsation of the adjacent artery walls might cause PVS CSF to flow. The speed of the arterial wall pushing against the PVS correlated with the flow velocity of the CSF.
This normal healthy flow can be compared to CSF flow when there is a high blood pressure, which causes arteries to flex and stiffen against the blood. Angiotensin II was a drug used on the mice to increase their blood pressure, which resulted in the arteries changing their motion, which resulted in the slowing down of the flow in the PVS. Not only was the flow slower, but the CSF sometimes flowed in the backwards direction. This is important because high blood pressure is known to be associated with an increased risk of Alzheimer’s disease and this may provide a mechanism for why and a potential target for treatments.
I think this seminar was great because it connected a potential mechanism for how high blood pressure can possibly lead to Alzheimer’s disease by studying the glymphatic system. I hope we will soon have data not only on mice but on humans, so the evidence is clearer in how it relates to human health. There is also still the question that needs to be answered on how short-term high blood pressure compares to chronic high blood pressure when the glymphatic system is disrupted. Also, I would want to know more about how this disrupted flow contributes to disrupted clearance of metabolic waste.