Hydrocephalus is the second most common congenital anomaly affecting the developing human nervous system with an estimated incidence of 1 per 1,000 live births. Neonatal hydrocephalus leads to the accumulation of cerebrospinal fluid (CSF) and to dilated ventricles around the time of birth, resulting in significant neurological deficits and mortality. There are different causes of hydrocephalus during development including primary (genetic) and secondary (hemorrhage, infection, or trauma). While some cases of hydrocephalus have an inciting event, a large percentage of congenital cases are of an unknown etiology. There has been little progress in understanding the idiopathic causes of neonatal hydrocephalus. In particular, the cellular events that lead to the development and progression of idiopathic neonatal hydrocephalus are poorly understood.
There is also a significant cost to the medical care system that results from hydrocephalus. There is an estimated 2 billion dollar annual cost for treating hydrocephalic patients with CSF shunts that are prone to malfunction, necessitating multiple surgeries. Hydrocephalus accounts for approximately 2% of all pediatric hospital stays and 3% of all pediatric hospital charges. Hydrocephalus is also associated with high mortality rates in neonates despite advances in diagnosis. Moreover, treatment of infants affected by hydrocephalus is still reliant on invasive surgery. With little progress in the research on hydrocephalus, identifying molecular mechanisms underlying this disease is a high priority for our research group.
Recently, our mouse models with impaired cilia function have provided novel insight into the mechanisms involved in hydrocephalus occurring in the absence of obstruction, a condition known as communicating hydrocephalus. It has been proposed that mutations in cilia-related genes disrupt motile cilia structure and function, which in turn leads to defective beat mechanics in ependymal cells and abnormal flow of CSF. Innovative discoveries by our group, however, have shown that mechanisms in the development of neural stem cells from altered primary cilia signaling is responsible for, but not a consequence of, neonatal hydrocephalus. Read more about our discoveries.