Working in a mouse model of hydrocephalus, the research team honed in on a specific group of immature cells called neural precursor cells (NPCs) that give rise to most types of brain cells, including neurons and glia cells. One particular subgroup of NPCs, which has only recently been identified and is involved in the development of normal ventricles, became the focus of the team's study.
During brain development, this population of immature cells proliferates and dies off in a precisely coordinated process to produce normal ventricles.
The team discovered an imbalance in the proliferation and survival of these cells, which leads to hydrocephalus in the experimental mouse model.
The imbalance is caused by problems in signaling pathways that prompts these NPCs to die or to proliferate. Both processes are abnormal in the mouse model the cells died at twice the rate seen in normal mouse brains and proliferated at only half the normal rate.
Having identified the problem, the researcher then showed that treatment with lithium bypasses one aspect of the abnormal signaling and restores normal proliferation of the precursor cells, which in turn reduces the hydrocephalus in the mice.
"Our findings demonstrate for the first time that neural progenitor cells are involved in the development of neonatal hydrocephalus," Carter says. "We are also the first to manipulate the development of these progenitor cells and successfully treat neonatal hydrocephalus, a feat which opens the door to novel treatment strategies in treating this disease and other neurological diseases."
Because the study identifies cell signaling defects as a cause of hydrocephalus, the findings pave the way for identification of additional signaling pathways involved in the development of this disease, and lay the groundwork for developing non-invasive therap
|Contact: Jennifer Brown|
University of Iowa Health Care