Brain fluid flow may underlie neurodevelopmental disorders

Brain fluid flow may underlie neurodevelopmental disorders

Disrupted flow of brain fluid may cause neurodevelopmental disorders as a new imaging technique reveals circulation patterns in developing brain

The brain floats in a sea of fluid that cushions it against injury, supplies it with nutrients and carries away waste. Disruptions to the normal ebb and flow of the fluid have been linked to neurological conditions including Alzheimer’s disease and hydrocephalus, a disorder involving excess fluid around the brain.

Researchers at Washington University School of Medicine in St Louis created a new technique for tracking circulation patterns of fluid through the brain and discovered, in rodents, that it flows to areas critical for normal brain development and function.

Further, the scientists found that circulation appears abnormal in young rats with hydrocephalus, a condition associated with cognitive deficits in children.

The findings suggest that the fluid that bathes the brain — known as cerebrospinal fluid — may play an under-recognised role in normal brain development and neurodevelopmental disorders.

Senior author Jennifer Strahle, MD, an associate professor of neurosurgery, of paediatrics, and of orthopaedic surgery, said: “Disordered cerebrospinal fluid dynamics could be responsible for the changes in brain development we see in children with hydrocephalus and other developmental brain disorders.”

As a paediatric neurosurgeon, Strahle treats children with hydrocephalus at St Louis Children’s Hospital.

She added: “There’s a whole host of neurologic disorders in young children, including hydrocephalus, that are associated with developmental delays.

“For many of these conditions we do not know the underlying cause for the developmental delays.

“It is possible that in some of these cases there may be altered function of the brain regions through which cerebrospinal fluid is circulating.”

See also: Obesity linked to poor brain health in children


Much research has been conducted mapping the drainage of cerebrospinal fluid in the brains of adults. However, it is not well known how cerebrospinal fluid interacts with the brain itself.

Cerebrospinal fluid pathways in the brain likely vary with age, as young children have not yet developed the mature drainage pathways of adults.

Strahle; first author Shelei Pan, an undergraduate student; and colleagues developed an X-ray imaging technique using gold nanoparticles that allowed them to visualise brain circulation patterns in microscopic detail.

Using this method on young mice and rats, they showed that cerebrospinal fluid enters the brain through small channels primarily at the base of the brain, a route that has not been seen in adults. In addition, they found that cerebrospinal fluid flows to specific functional areas of the brain.

Strahle said: “These functional areas contain specific collections of cells, many of which are neurons, and they are associated with major anatomic structures in the brain that are still developing.

“Our next steps are to understand why cerebrospinal fluid is flowing to these neurons specifically and what molecules are being carried in the cerebrospinal fluid to those areas.

“There are growth factors within the cerebrospinal fluid that may be interacting with these specific neuronal populations to mediate development, and the interruption of those interactions could result in different disease pathways.”

brain bleed

Further experiments showed that hydrocephalus reduces cerebrospinal fluid flow to distinct neuron clusters.

Strahle and colleagues studied a form of hydrocephalus that affects some premature infants. Babies born prematurely are vulnerable to brain bleeding around the time of birth, which can lead to hydrocephalus and developmental delays.

Strahle and colleagues induced a process in young rats that mimicked the process in premature babies. After three days, the tiny channels that carry cerebrospinal fluid from the outer surface of the brain into the middle were fewer and shorter, and circulation to 15 of the 24 neuron clusters was significantly reduced.

She explained: “The idea that cerebrospinal fluid can regulate neuronal function and brain development isn’t well explored.

“In the setting of hydrocephalus, it’s common to see cognitive dysfunction that persists even after we successfully drain the excess fluid.

“The disordered cerebrospinal fluid dynamics to these functional regions of the brain may ultimately affect brain development, and normalising flow to these areas is a potential approach to reducing developmental problems.

“It is an exciting field, and we are only at the beginning of understanding the diverse functions of cerebrospinal fluid.”

The findings are available online in Nature Communications.

Image: The addition of a magenta tracer molecule illustrates the flow of fluid around the brain, revealing that neurons in the hippocampus (cyan), the brain’s memory centre, are awash in fluid. Researchers at Washington University School of Medicine in St Louis have discovered that this fluid flows to areas critical for normal brain development and function, suggesting that disruptions to its circulation may play an under-recognised role in neurodevelopmental disorders. © Shelei Pan and Peter Yang/ Washington University.

Leave a reply

Your email address will not be published. Required fields are marked *

Aether: Issue 3 Feb 2023

Aether: Issue 2 Nov 2022

Aether: Issue 1 Aug 2022

Subscribe for free

Latest Testimonial

What a beautiful motto: Discoveries must be read and not just published. When I was contacted by Aether as a new digital service to share scientific and technological insights I had my doubts that this was really going to be according to what I call the “open source & makers’ spirit”: knowledge should be free and it is there to be shared.

Well, Aether is faithful to its motto and shares discoveries freely. It has been a pleasure to collaborate for the interview and subsequent article. It has been greatly self satisfying to see how the interview was professionally and truthfully redacted and then published. Sharing thoughts and sparks for discussions is fundamental to the progress of society. Your journal offers clarity and brevity and I believe it provides the sparks to ignite any reader whether academic or not into action.

Dr Maria-Cristina Ciocci
Co-founder and Manager of non-profit organisation De Creative STEM,GirlsInSTEM