Spinal Cord Research Award funded by Marjorie Grace Lawn Estate
Hydrocephalus and the role of brain water channels.
Dr Brian Owler
Neurosurgeon Children’s Hospital at Westmead, Discipline of Paediatrics and Child Health, University of Sydney
Co-Investigator: Dr Dongwei Wang
Hydrocephalus is an important neurosurgical condition in which cerebrospinal fluid accumulates in the ventricular system of the brain. It affects all ages and is the most common reason for paediatric neurosurgical admission besides trauma. Hydrocephalus may be congenital but is also a common sequalae of a variety conditions including intracranial haemorrhage, meningitis and surgery. Unless treated it causes delayed development and/or neurological impairment. It may cause death. Current treatments are surgical and usually involve a CSF shunt or endoscopic third ventriculostomy. Shunts commonly fail (30% with 1 year) due to blockage and infection resulting in shunt revision surgery. Alternative effective medical treatments are needed. This requires an improved understanding of CSF physiology.
Hydrocephalus occurs when CSF production exceeds CSF absorption capacity (eg scarring of arachnoid villi or subarachnoid space secondary to haemorrhage or infection) or where there is an obstruction to CSF outflow (eg intracranial neoplasm). The choroid plexus is a vascular structure located within the cerebral ventricles where the majority of CSF production occurs. Aquaporins are a family of water channel forming proteins. Aquaporin 1 (AQP1) is found in the apical membrane of choroid plexus epithelial cells and is considered to have a role in CSF production.
Our laboratory has developed a cisternal kaolin model of hydrocephalus in the mouse. The aims of this project are to characterise this model in terms of its neuropathology and to determine whether choroidal AQP1 is altered in hydrocephalic mice compared to controls. In addition, we aim to determine whether AQP1 knockout mice develop hydrocephalus after cisternal injection of kaolin. It is anticipated that this project will define the importance of choroidal AQP1 in the development of hydrocephalus and its potential as a therapeutic target.