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

Researchers at Washington University School of Medicine in St. Louis created a recent 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 performance. Further, the scientists found that circulation appears abnormal in young rats with hydrocephalus, a condition related to cognitive deficits in children.

The findings, available online in Nature Communications, suggest that the fluid that bathes the brain -; generally known as cerebrospinal fluid -; may play an underrecognized role in normal brain development and neurodevelopmental disorders.

“Disordered cerebrospinal fluid dynamics may very well be chargeable for the changes in brain development we see in children with hydrocephalus and other developmental brain disorders,” said senior creator Jennifer Strahle, MD, an associate professor of neurosurgery, of pediatrics, and of orthopedic surgery. As a pediatric neurosurgeon, Strahle treats children with hydrocephalus at St. Louis Kid’s Hospital. “There’s an entire host of neurologic disorders in young children, including hydrocephalus, which can be related to developmental delays. For a lot of these conditions we have no idea the underlying cause for the developmental delays. It is feasible that in a few of these cases there could also be altered function of the brain regions through which cerebrospinal fluid is circulating.”

Much research has been conducted mapping the drainage of cerebrospinal fluid within the brains of adults. Nonetheless, it just isn’t well-known how cerebrospinal fluid interacts with the brain itself. Cerebrospinal fluid pathways within the brain likely vary with age, as young children haven’t yet developed the mature drainage pathways of adults.

Strahle; first creator 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 bottom of the brain, a route that has not been seen in adults. As well as, they found that cerebrospinal fluid flows to specific functional areas of the brain.

These functional areas contain specific collections of cells, a lot of that are neurons, and so they are related to major anatomic structures within the brain which can be still developing. Our next steps are to grasp why cerebrospinal fluid is flowing to those neurons specifically and what molecules are being carried within the cerebrospinal fluid to those areas. There are growth aspects inside the cerebrospinal fluid which may be interacting with these specific neuronal populations to mediate development, and the interruption of those interactions could result in numerous disease pathways.”

Jennifer Strahle, MD, associate professor of neurosurgery, of pediatrics, and of orthopedic surgery

Further experiments showed that hydrocephalus reduces cerebrospinal fluid flow to distinct neuron clusters. Strahle and colleagues studied a type of hydrocephalus that affects some premature infants. Babies born prematurely are vulnerable to brain bleeding across the time of birth, which may result in hydrocephalus and developmental delays. Strahle and colleagues induced a process in young rats that mimicked the method in premature babies. After three days, the tiny channels that carry cerebrospinal fluid from the outer surface of the brain into the center were fewer and shorter, and circulation to fifteen of the 24 neuron clusters was significantly reduced.

“The concept that cerebrospinal fluid can regulate neuronal function and brain development is not well explored,” Strahle said. “Within the setting of hydrocephalus, it is common to see cognitive dysfunction that persists even after we successfully drain the surplus fluid. The disordered cerebrospinal fluid dynamics to those functional regions of the brain may ultimately affect brain development, and normalizing flow to those areas is a possible approach to reducing developmental problems. It’s an exciting field, and we’re only initially of understanding the varied functions of cerebrospinal fluid.”

Source:

Washington University School of Medicine

Journal reference:

Pan, S., et al. (2023) Gold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation within the brain. Nature Communications. doi.org/10.1038/s41467-023-36083-1.