New Technology Sheds Light on CSF Flow Through the Brain
Iliff JJ, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med.2012;4(147):147ra111.
How does the human brain clear waste products without a lymphatic system? Researchers who investigated this issue at the Center for Translational Neuromedicine at the University of Rochester Medical Center in New York have identified paravascular channels along which cerebrospinal fluid (CSF) flows, clearing the brain of the waste products of cellular metabolism. These channels were observed in 4 mice with brains that contained water channel aquaporin-4 (AQP4) in their astrocytes. Three mice with brains that lacked AQP4 had much slower CSF flow and solute clearance.
The researchers used an advanced technology called in vivo 2-photon imaging, which used laser scanning microscopy to visualize radiolabeled substances in real time. Small fluorescent tracer molecules injected into the cerebral ventricles of the mice showed very little perfusion beyond the injection site. When the tracer was injected into the subarachnoid space, paravascular CSF flow quickly spread throughout the brain. An ex vivo approach was used to map paravascular CSF flow; the tracer exited the brain, primarily along the medial internal cerebral veins or the lateral-ventral caudal rhinal veins. These findings confirm the results of recent studies1-3 that described CSF flow as something other than the classic secretion by the choroid plexus and resorption by the arachnoid villi.
The great detail of the methods used in this study are too numerous and complex to describe in the present review, but the highlights of the results for the researchers were (1) that it is now possible to describe how brain parenchyma clears waste products without lymphatics and (2) that this clearing of waste occurs via the flow of CSF in the extracellular space. Also, mice brains that did not have these paravascular channels because they did not carry the AQP4 gene cleared amyloid-β at approximately a 70% reduced rate. The authors report the relationship between Alzheimer disease and amyloid-β and suggest that this pathway may remove amyloid-β from the central nervous system, thus providing guidance in the continued attempts to combat Alzheimer disease.
This article was selected for review because of its relevance for neuroscience in general and for osteopathic concepts in particular. The finding that CSF flows in cerebral extracellular paravascular space is an advancement in the understanding of CSF flow dynamics and, while not mentioned in the article, may be useful in the understanding and treatment of hydrocephalus or other intracranial pathologies such as subdural hematoma resolution.
The osteopathic medical profession includes the practice of cranial osteopathic manipulative treatment. In my opinion, science has only begun to penetrate the surface and function of the brain and its fluid dynamics with this study and others reviewed in these pages.4-7 Osteopathic physicians who use cranial osteopathic manipulative treatment have long thought that the application of manually guided forces on cranial structures enhances the flow of CSF.
In particular, the compression of the fourth ventricle (CV4) technique is thought, among other effects, to enhance intracranial CSF flow. Assuming that these findings on mouse brains are indeed applicable to human brains, as the authors of this article assert, then the possibility of enhanced CSF flow by application of the CV4 technique may be an important clinical tool with several possible implications. To say that the CV4 technique may be helpful in the prevention of Alzheimer disease by means of the enhanced clearance of amyloid-β is indeed speculative at best, but it is a possibility worthy of future research and discussion. —H.H.K.
References
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© 2012 The American Osteopathic Association
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Articles in the same Issue
- Letters
- Holding Rhetoric to a New Standard: What's the P Value of That Statement, Senator?
- Joining Forces: Military Perspectives for Osteopathic Medical Education
- Editorial
- Introducing the JAOA's New Online Manuscript Tracking System
- The Somatic Connection
- Self-Treatment of Myofascial Trigger Points Relieves Chronic Pelvic Pain
- Empirical Measurement of the Effects of Myofascial Release in Cervical and Lumbar Regions
- OMT and Obesity: A Timely Topic
- Myofascial Release Combined With Physical Therapy Improves Venous Blood Flow
- New Technology Sheds Light on CSF Flow Through the Brain
- Original Contributions
- C-Reactive Protein as a Predictor of Chorioamnionitis
- Research Funding at Colleges of Osteopathic Medicine in the United States
- The Role of Social Networking Web Sites in Influencing Residency Decisions
- Brief Report
- Combined Manual Therapy Techniques for the Treatment of Women With Infertility: A Case Series
- Case Report
- Carbon Monoxide Poisoning Secondary to Hookah Smoking
- Clinical Images
- A Curious Case of Recurrent Pneumonia
- In Your Words
- A Step Outside
- CME Quiz
- CME Quiz
