Fluid filled. compared to a healthy human fetus ( left ), a fetus with hydrocephalus can not drain the fluid he needs from his brain.
J. P. McAllister Science Translational Medicine
Many premature babies suffer from bleeding in their brains still developing. Even when the bleeding stops, another condition of life in danger can strike hydrocephalus, which occurs when the fluid to keep the brain healthy built because it can not drain properly. For decades, doctors have known that were related hemorrhage and hydrocephalus, also known as "water on the brain", but they were not sure why. A new study suggests that the answer lies in a lipid that is common in the blood, but can also severely disrupt the structure and brain function when present in large quantities.
hydrocephalus affects about one in 1,500 babies, and treatment is imperfect. the doctors implant usually a shunt to drain cerebrospinal fluid from the brain and spinal cord. Shunts fail over time, however, and monitoring surgeries are sometimes necessary. the state itself can also cause neurological problems life. the roots of hydrocephalus remain cloudy, but for those that are related to brain bleeds, the assumption was that the blood-clots necessary to stop bleeding-blocked roads razor-thin through which cerebrospinal fluid must travel to exit the brain. "We have assumed for 100 years it was just a mechanical block," says James McAllister II, a neuroembryologist at the University of Utah School of Medicine in Salt Lake City, who was not involved in the work Recent. "Everyone thought you dammed the narrow channels."
A group based at the Scripps research Institute in San Diego, California, recently began to suspect something else was at work. for years, Scripps neuroscientist Jerold Chun had studied embryonic brain and how certain fats in the blood of the mother and the embryo affect its development. He and graduate student Yun Yung has developed a way to inject one of these lipid lysophosphatidic acid (LPA) in the ventricles of the brain of fetal mouse When they did, they saw something surprising.. Each embryo that got the injection was born with hydrocephalus
researchers have experienced before injecting the blood into the brain of animals to mimic bleeding, and had indeed observed the appearance of hydrocephalus. But they had not isolated the specific molecular components of blood as the key. To determine if the LPA was he, Chun and colleagues repeated mouse brain injections with only red blood cells. (APL is in the plasma component of blood). This did not cause hydrocephalus, but the injection of plasma made in some animals. And genetically remove specific LPA receptor prevented the blood of the inducing condition.
In a final experiment, the group gave the animal a compound that prevents the LPA to bind to its receptor on brain cells of mice just before they were injected with hydrocephalus inducing LPA. These mice remained healthy, the researchers report today Science Translational Medicine .
Why LPA have this effect? "It's almost like a drug overdose," says Chun. LPA receptors are all on neural progenitor cells, which go to form neurons and other cell types in the brain of a young. When a flood of LPA strikes, "it leads them to do things they would not do." This results in changes in brain structure as a form and movement of cells from which they are supposed to be, including those lining the ventricles and help control the flow of fluid.
hydrocephalus researchers, who have long been frustrated by the slow progress of the field, are enthusiastic. "It really blew me away," says McAllister work. "This is the first time that we recognized that there are bad things in the blood that can affect cells" and cause hydrocephalus.
Although the work has been done only in mice and should be confirmed, there is hope that it will be. the LPA receptor is expressed in the brains of human fetuses, as in mice, and in the same types of neural progenitor cells. "This is good news," said Pat Levitt, a neuroscientist at the University of Southern California in Los Angeles. "Is it a conclusion as will be linked to the human condition? ... I think in a case like this, it is fair to say yes."
Equally exciting is the discovery provides a clear path to therapy. Although there is no LPA receptor blocker on the market at the moment, proteins fall into a class that is usually covered by the drug. In theory, a compound like this might be given to premature babies from birth in an effort to prevent hydrocephalus should bleed a brain occurs, or for pregnant women whose fetuses are at risk because of hydrocephalus bleeding. Chun The group began to study the cerebrospinal fluid and other human samples, to see what the PLA is doing there.
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