The Kids Neurosurgical Research Unit was established to enable to basic science research into a range of paediatric neurosurgical conditions. Current research areas include hydrocephalus, paediatric brain tumours and spinal cord injury. The work of the laboratory has focussed on the relationship between these conditions and aquaporins. Aquaporins are a group of molecules that act as water channels in the plasma membranes of cells. AQP1 and 4 are the main aquaporins in the brain and facilitate the drainage from or accumulation of water within the brain. Through the study of AQPs the Kids Neurosurgical Research Unit aims to increase our understanding of these conditions and develop novel treatments to ultimately improve clinical outcomes for patients and their families.
Hydrocephalus is the focus of this laboratory’s research. It is a common neurological condition in which cerebrospinal fluid (CSF) accumulates within the ventricles of the brain causing neurological dysfunction and damage to the developing brain. If allowed to persist it can cause developmental delay, reduced level of consciousness or even death. The most common reason for hydrocephalus is a problem with CSF absorption due to a blockage (eg tumour) or scarring of the absorption mechanisms (eg infection or bleeding). Current treatment most commonly involved the use of a shunt. While potentially life-saving shunt have a relatively high rate of failure requiring revision surgery. This has its own set of morbidity and even mortality. Endoscopic procedures can avoid the use of a shunt but are not applicable for every patient and have their own failure rate.
Through the study of aquaporins the laboratory has focussed on developing a non-surgical treatment for hydrocephalus. AQP1 which is found in the choroid plexus is a promising therapeutic target. AQP1 in the choroid plexus has a significant role in CSF production. There are no non-toxic pharmaceutical agents to block AQP1 and therefore reduce CSF production. We have studied AQP1 in the choroid plexus of the mouse both in health and in a model of hydrocephalus and confirmed its therapeutic potential. We are studying gene therapy, specifically a gene silencing technique, in order to reduce AQP1 expression in the choroid plexus and therefore treat or prevent hydrocephalus.
Altered cellular localization of aquaporin-1 in experimental hydrocephalus in mice and reduced ventriculomegaly in aquaporin-1 deficiency.
Wang D, Nykanen M, Yang N, Winlaw D, North K, Verkman AS, Owler BK.
Mol Cell Neurosci. 2011 Jan;46(1):318-24. Epub 2010 Oct 30.
Expression of AQP1 and AQP4 in paediatric brain tumours.
Wang D, Owler BK.
J Clin Neurosci. 2011 Jan;18(1):122-7. Epub 2010 Oct 20
Aquaporins: relevance to cerebrospinal fluid physiology and therapeutic potential in hydrocephalus.
Owler BK, Pitham T, Wang D.