Cerebrospinal fluid flow in the brain

Adi Raghunandan, Postdoctoral Research Associate, Kelley Group

Friday, May 7, 2021
1:30 p.m.

Diseases such as Alzheimer’s (AD) are linked to the toxic build-up of waste products produced in the brain during cellular activity. As a part of the glymphatic system, cerebrospinal fluid (CSF) has been found to flow around and into the brain, removing these toxins to maintain the brain’s health. In this talk, I will present results on cerebrospinal fluid transport in the entry and exit pathways of the glymphatic system. Combining biological experiments that peer into the brains of live mice with the engineering technique of particle tracking, I will show that CSF enters the brain naturally, propelled by the pulsation of the nearby arteries. This notion has been controversial, with several suggestions that the observed flows are unnatural and artificially driven by the tracer injection process. The results I present resolve this controversy and have significant clinical relevance as the glymphatic circulation has been proposed as a unique method to deliver drugs into the brain.


Next, I will show that these biological and engineering techniques can be adapted to study the flow of CSF exiting the glymphatic system through the cervical lymph vessels of the neck. Assessing fluid transport in these vessels has been restricted to studies of isolated vessels that are artificially pressurized to drive fluid flow. These conditions do not accurately represent physiological transport, where a network of vessels is thought to undergo coordinated pulsations to transport fluid.  However, evidence for this dominant driving mechanism remains elusive. I will present measurements that are the first of their kind to confirm that the intrinsic pulsations of lymphatic vessels are the primary drivers of physiological fluid transport. Furthermore, I will present evidence that these pulsations deteriorate with age, severely reducing fluid clearance and presenting a bottleneck in fluid transport. Finally, I will show that administration of prostaglandin-alpha (PGF-2α), a drug that stimulates vessel pulsation, can partially restore and improve fluid clearance.