Cerebrospinal Fluid Disorders Research Group

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Group leader: Dr Alexandra Sinclair

Overview

Cerebrospinal fluid (CSF) bathes the brain and spinal cord and is vital for the maintenance of fluid homeostasis within the central nervous system. Understanding the pathophysiology of CSF disorders is key to improve its diagnosis and management as well as to develop novel therapy approaches.

Our research group

Cerebrospinal fluid is continuously produced by the choroid plexus in the lateral, third and fourth ventricles. It flows through the ventricular system, draining through basal cisterns of the brain, bathing the spinal cord and then reabsorbed into the blood circulation. 

The production of CSF by the choroid plexus is tightly regulated providing the necessary nutrients and removing any waste which may compromise the normal homeostasis of the central nervous system. Because the CSF bathes the brain and spinal cord, it provides buoyancy protecting them from trauma. The CSF is vital for the maintenance of a stable intracranial pressure by compensating for changes of increased intracranial blood pressure.

Our research group is thus interested in understanding the molecular, cellular and physiological mechanisms underlying CSF disorders. The ultimate aim is to develop strategies to improve diagnosis, management and development of novel therapeutic approaches.

Our research group has a diverse range of interests which include evaluation of intracranial pressure dynamics, particularly focusing on idiopathic intracranial hypertension; development of chronic communicating hydrocephalus after subarachnoid haemorrhage; Growth factors and novel peptide hormones in fluid homeostasis; management and outcome of post-traumatic syringomyelia.

Current Projects

  • Sustained treatment of Idiopathic Intracranial Hypertension (IIH) through weight loss induced by bariatric surgery (IIH:WT, NIHR funded)
    http://clinicaltrials.gov/show/NCT02124486)
  • Assessing the therapeutic efficacy of an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor (AZD4017) in idiopathic intracranial hypertension (IIH) (IIHDT, MRC funded) (http://clinicaltrials.gov/show/NCT02017444)
  • Creation of UK Idiopathic Intracranial Hypertension database
  • Establishing in vitro  choroid plexus epithelial and arachnoid granulation cell functional model systems of CSF secretion and drainage (funded by 'Midland Neuroscience Research Fund')
  • Investigating the role of TGF-β1 in the development of chronic communicating hydrocephalus after subarachnoid haemorrhage: Post-haemorrhagic communicating hydrocephalus is a common complication of intraventricular haemorrhage in premature infants, which often requires permanent ventricular shunting to avert the development of chronic neurological symptoms. We are exploring novel therapeutic strategies to prevent the development of hydrocephalus and improve the outcomes for these infants. 

Recent Publications

Staff

Principal Investigators
Dr Alexandra Sinclair
Dr Ana Maria Gonzalez

Clinical Research Fellow
Dr Keira Annie Markey
Dr Mazen Sabah

Research Fellow
Dr Hannah Botfield

Honorary Staff
Dr Susan Mollan - University Hospitals Birmingham NHS Trust, UK
Dr Graham Flint - University Birmingham Hospitals NHS Trust, UK

Internal Collaborators
Professor Ann Logan - School of Clinical and Experimental Medicine
Professor Carl Clark - School of Clinical and Experimental Medicine
Professor Kim Shapiro - School of Psychology
Dr John Curnow - School of Immunity and Infection
Professor Tony Belli - School of Clinical and Experimental Medicine

External Collaborators
Professor Jeremy Tomlinson – University of Oxford, UK
Professor Paul Stuart – University of Leeds, UK
Dr Hitesh Sanganee - AstraZeneca
Professor Mark Wagshul - Albert Einstein College of Medicine in New York, USA
Prof Filip Krag Knop, Gentofle Hospital, University of Copenhagen
Prof Pat McAllister – Washington University at St Louis, USA
Dr Tim Matthews - University Hospitals Birmingham NHS Trust, UK
Dr Mike Burdon - University Hospitals Birmingham NHS Trust, UK
Professor Gordon Plant - The National Hospital and Moorfields Eye Hospital, University College London Hospitals, UK
Mrs Susan Mollan - University Hospitals Birmingham NHS Trust, UK
Mr Andrew Jacks - University Hospitals Birmingham NHS Trust, UK
Professor Conrad Johanson - Brown University, USA
Professor Andrew Baird - University of California San Diego, USASubmit with Message
Dr Brian Eliceiri - University of California San Diego, USA
Mr Paul Super - Heart of England Fundation Trust, UK
Daniel Ray - Director of Informatics University Hospitals Birmingham, UK