• The Pulse

“No Pressure at All”: Caltech-UCI Novel Clinical Research on Normal Pressure Hydrocephalus

Updated: Jul 15, 2019

Author: Jaeyoung Kang


The Chen Lab at UC Irvine Medical Center, led by neurosurgeon and Caltech alumnus Dr. Jeff Chen, conducts clinical research on the treatment of normal pressure hydrocephalus (NPH). While juggling the responsibilities of the operating room, the clinic, and the conference hall, Dr. Chen finds time to be inside the research facilities of Edward Shanbrom Hall, guiding the efforts of his lab as his student scientists work tirelessly on different projects.


An MRI image showcasing the difference between a neurotypical and NPH brain.

Although the Chen Lab is involved with many endeavors at once, all of them are related to efforts for improving conditions in NPH patients, who are Dr. Chen’s most frequent visitors in the clinic. The hallmark sign of NPH is the accumulation of a bodily substance called cerebrospinal fluid (CSF) in spaces in the brain known as ventricles. CSF is normally circulated through the brain and reabsorbed by the body, which provides important functions such as waste removal and maintenance of healthy pressure levels. In NPH patients, however, this liquid does not drain properly from the brain, instead accumulating in the brain’s cavities. The result is that pressure is exerted on the brain, causing negative symptoms such as headaches, gait loss, problems with bladder control, and dementia.


“Really, it’s easy to conceptualize if you think of it like a water balloon. If you fill a balloon with water, it exerts pressure on the plastic. Same principle here,” Dr. Chen concisely explains.


The brain's lymphatic system.

Although there are numerous theories regarding the biomechanics of NPH, the one the Chen Lab is most concerned with involves the activities of the dural lymphatic vessels, which are currently a relatively new topic in clinical research. It was recently discovered that the dura mater, one of the membranes surrounding the brain, has lymphatic vessels that transport CSF directly to the lymphatic system for reabsorption. The fact that the brain’s CSF flow has a direct connection to the lymphatic system is by itself groundbreaking. It suggests that there is an efficient path by which cerebral toxins and waste products are removed that was, until recently, unknown to medical science. Taking it a step further, however, the Chen Lab hopes to demonstrate that the dural lymphatic system plays an active physiological role in the maintenance of normal CSF flow.


Several avenues of research have come up involving dural lymphatics and the improvement of treatment procedures in conditions related to abnormal CSF flow. Working in the Chen Lab, I have been tasked to develop a new mathematical model to describe CSF flow, taking into account the presence of dural lymphatics. Additionally, I am also analyzing real-time data from various traumatic brain injury (TBI) patients to monitor various parameters, from brain oxygenation levels to intracranial pressure. As NPH is theorized to be a long-term consequence that arises from TBI, the hope is that this investigation will capture novel statistical trends that can shed some light on how the abnormal CSF accumulation in NPH is related to the damage caused by injury to the brain.


Fellow Caltech researcher Anna Tifrea is getting her hands wet as well, as she works with me to map out the lymphatic pathways within dura mater samples. To better understand the connection between the brain’s membranes and the lymphatic system, we are attempting to track cells that line the lymphatic vessels in the membranes. As a novel approach to research on dural lymphatics, we are also aiming to detect extracellular vesicles called exosomes, which are present in CSF and thus may be present in the dural lymphatic vessels as well. Exosomes can be thought of as tiny membrane-bound packages of proteins or other macromolecules. Lately, they have been implicated as propagators of harmful molecules such as β-amyloid in neurodegenerative disorders such as Alzheimer’s disease. Establishing the presence of these particles in dural lymphatic samples could allow for a more complete map of CSF flow between the brain and the lymphatic system, while also offering new information about how the brain clears toxic molecules in dementias that exhibit similar symptoms as NPH.


A stain from the Chen Lab's research.

Though the amount of work that needs to be done appears large, the Chen Lab undertakes it with no pressure at all (pun intended).

“Real doctors don’t take breaks,” Dr. Chen remarks with a soft yet confident grin.


Picture citations:

https://www.saturdayeveningpost.com/2013/05/normal-pressure-hydrocephalus/

http://www.sci-news.com/biology/human-brain-lymphatic-system-05288.html

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