Cerebrospinal Fluid Disorders Research Group

Sinclair---CSF-Disorders-picture-V2

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.
  • Assessing the therapeutic efficacy of an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor (AZD4017) in idiopathic intracranial hypertension (IIH).
  • The role of steroid hormones and 11beta hydroxysteroid dehydrogenase type 1 in intracranial pressure regulation in collaboration with Professor Paul Stewart (CEDAM, School of Clinical and Experimental Medicine).
  • Creation of UK Idiopathic Intracranial Hypertension database
  • 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.
  • Neuroendocrine control of brain homeostasis: We are interested in understanding the role that growth factors and other novel peptide hormones may play in CNS homeostasis after trauma. A case of point is a newly recognised neuropeptide encoded by the oesophageal related gene-4 (Ecrg4). Our studies clearly suggest this peptide  (augurin) plays a role in CSF homeostasis.

Recent Publications

Staff

Principal Investigators
Professor Ann Logan
Professor Carl Clark
Dr Ana Maria Gonzalez
Dr Alexandra Sinclair

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

Clinical Research Fellow
Dr Keira Annie Markey

Research Fellow
Dr Hannah Botfield

External Collaborators
Dr Tim Matthews - University Hospitals Birmingham NHS Trust, UK
Dr Mike Burdon - University Hospitals Birmingham NHS Trust, UK
Dr Susan Mollan - University Hospitals Birmingham NHS Trust, UK
Prof Pat McAllister - University of Utah, USA
Prof Conrad Johanson - Brown University, USA
Prof Andrew Baird - University of California San Diego, USA
Dr Brian Eliceiri - University of California San Diego, USA