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Scripps research scientists find clue to cause of childhood hydrocephalus
Date:9/7/2011

atory specializes in the study of lipid-signaling molecules involved in the developing brain, including LPA. LPA is normally produced in the fast-growing fetal brain, and appears to be important for the normal development of neural "progenitor" cells. But when the researchers added abnormally high concentrations of LPA to the brains of fetal mice, they found an unexpected effect on brain development. "When we looked at their condition as newborns, we were surprised to see that they uniformly had big, fluid-filled brains," said postdoctoral fellow Yun Yung, PhD. "It was a Eureka moment, because we realized that LPA might help explain hydrocephalus."

Reviewing the medical literature on the condition, Chun and Yung noted that it was often linked to brain-bleeding events in the womb and typically also featured some improperly developed brain structures. "Our experiments with LPA connected both sets of findings," said Yung, "because LPA is involved in blood clotting and can reach very high concentrations during hemorrhages; plus, our LPA-exposed mouse brains had structural abnormalities like those reported in human cases."

Cerebrospinal fluid cushions the brain, provides it with basic nutrients, and is normally produced by the membrane-like choroid plexus within the fluid-filled chambers of the brain known as ventricles. Ependymal cells that line these ventricles have hair-like extensions that are thought to promote the normal flow of fluid. "In our LPA-exposed mice, there were patches in the ventricular lining where these ependymal cells were missing, which could have led to a disruption of the normal cerebrospinal fluid flow," said Yung. Structures in the ventricles that normally permit the proper drainage of fluid also appeared to be partly blocked by the improper overgrowth of cells, which might have further contributed to the brain-damaging fluid buildup.

The researchers were able to repeat these effects using the normal LPA-containing flu
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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