Neonatal hydrocephalus is a kind of nerve disorder resulting in growth and development of the cerebral ventricles. This problem is connected with significant morbidity and mortality that is frequently fatal otherwise treated. Hydrocephalus was described over 2500 previously by Hippocrates, the daddy of medicine, and stays poorly understood today. Current therapies still depend on invasive procedures developed over six decades ago which are connected wealthy in failure and complication rates. Thus, the identification of molecular mechanisms and the introduction of non-invasive treating neonatal hydrocephalus are high priorities for the medical and scientific communities. The current doctrine within the field is the fact hydrocephalus is only a “plumbing problem” introduced on by impaired cerebrospinal fluid (CSF) flow. Lately, animal models with impaired cilia have given understanding from the mechanisms connected with communicating (non-obstructive) hydrocephalus. However, because of a poor knowledge of hydrocephalus, no animal studies so far have identified a effective non-invasive treatment.

The objective of this thesis project should be to investigate molecular mechanisms underlying this problem and to identify a non-invasive, impressive treatment strategy.

In Chapter 2, we utilize a novel animal model with idiopathic hydrocephalus, mimicking a persons ciliopathy Bardet-Biedl Syndrome (BBS), to look into the a part of cilia in hydrocephalus. We uncover these rodents develop communicating hydrocephalus before the advancement of ependymal “motile” cilia, suggesting this phenotype develops because of structural “primary” cilia. Primary cilia are non-motile and lead to cellular signaling.

These results challenge the present dogma that structural motile cilia underlies neonatal hydrocephalus and implicate a manuscript role for primary cilia and cellular signaling during this disease.

Chapter 3 concentrates on identifying the url between primary cilia and neonatal hydrocephalus. During this chapter, we believe that disrupting the molecular machinery within primary cilia results in faulty PDGFR signaling and losing a specific type of neural progenitor cells known as oligodendrocyte precursor cells (OPCs). We uncover that losing OPCs results in neonatal hydrocephalus. Importantly, we know the molecular mechanism underlying both losing OPCs along with the pathogenesis of neonatal hydrocephalus.

Chapter 4 explores the therapeutic potential of individuals defective cellular signaling pathways to deal with neonatal hydrocephalus. By individuals faulty signaling, we restore normal advancement of oligodendrocyte precursor cells, and curtail the introduction of hydrocephalus. The task challenges the predominant check out hydrocephalus being strictly a “plumbing problem” treatable exclusively by surgical diversion of CSF. Here, we advise that hydrocephalus could be a neurodevelopmental disorder which can be ameliorated by non-invasive means. Importantly, we introduce novel molecular targets along with a non-invasive treatment method of this devastating disorder. For the understanding, we are the first one to effectively treat neonatal hydrocephalus in almost any model organism by targeting neural progenitor cells.

bardet-biedl syndrome, cilia, Hydrocephalus, lithium, neural progenitor cells, Oligodendrocyte precursor cells