by The brain swims in a sea of fluid that protects it from injury, nourishes it, and carries away waste. Disorders of the normal ebb and flow of fluid have been linked to neurological disorders, including Alzheimer’s disease and hydrocephalus, a disorder in which there is excess fluid around the brain.
Researchers at Washington University School of Medicine in St. Louis developed a new technique for tracking patterns of fluid circulation through the brain and discovered in rodents that it flows to areas critical to normal brain development and function. In addition, the scientists found that blood flow appears abnormal in young rats with hydrocephalus, a condition associated with cognitive deficits in children.
The results, available online in Nature Communications, suggest that the fluid that bathes the brain — known as cerebrospinal fluid — may play an underappreciated role in normal brain development and neurodevelopmental disorders.
“Disrupted cerebrospinal fluid dynamics may be responsible for the changes in brain development we see in children with hydrocephalus and other brain developmental disorders,” said senior author Jennifer Strahle, MD, associate professor of neurosurgery, pediatrics and orthopedic surgery. As a pediatric neurosurgeon, Strahle treats children with hydrocephalus at St. Louis Children’s Hospital. “There is a range of neurological disorders in young children, including hydrocephalus, that are associated with developmental delays. In many of these disorders, we do not know the underlying cause of the developmental delays. It is possible that in some of these cases there may be altered function of the brain regions through which CSF circulates.”
Much research has been done to map cerebrospinal fluid outflow in the adult brain. However, it is not known how cerebrospinal fluid interacts with the brain itself. CSF pathways in the brain likely vary with age, since young children have not yet developed the mature adult drainage pathways.
rays; First author Shelei Pan, an undergraduate student; and colleagues developed an X-ray imaging technique using gold nanoparticles that allowed them to visualize brain circulation patterns in microscopic detail. Using this method on young mice and rats, they showed that cerebrospinal fluid enters the brain mainly at the base of the brain through small ducts, a pathway that has not been observed in adults. In addition, they found that cerebrospinal fluid flows to specific functional areas of the brain.
“These functional areas contain specific collections of cells, many of which are neurons, and they are connected to important anatomical structures in the brain that are still developing,” said Strahle. “Our next steps are to understand why cerebrospinal fluid flows specifically to these neurons and what molecules in the cerebrospinal fluid are transported to these areas. There are growth factors in the cerebrospinal fluid that may interact with these specific neuronal populations to mediate development, and disrupting these interactions could lead to other disease pathways.”
Further experiments showed that hydrocephalus reduces CSF flow to different neuron clusters. Strahle and colleagues studied a form of hydrocephalus that affects some preterm infants. Premature babies are prone to cerebral hemorrhage 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 preterm infants. After three days, the tiny channels that carry cerebrospinal fluid from the outer surface of the brain to the center were fewer and shorter, and blood flow to 15 of the 24 neuron clusters was significantly reduced.
“The idea that CSF can regulate neuronal function and brain development hasn’t been well explored,” said Strahle. “In hydrocephalus, it is common to see cognitive dysfunction that persists even after the excess fluid has been successfully drained. The disrupted cerebrospinal fluid dynamics in these functional regions of the brain can ultimately impair brain development, and normalizing flow to these areas is a potential approach to reducing developmental problems. It is an exciting field and we are just beginning to understand the diverse functions of the cerebrospinal fluid.”
