BRAIN EXTRACELLULAR FLUID (ECF)

Brain Extracellular Fluid (Ecf)

Abstract

Acknowledgements

This thesis would not have been possible without the help of the people listed below. My sincere thanks go to all. I wish to thank especially:

The Violet Richards Charitable Trust and The Brain Research Trust for generously funding this research project.

My supervisors, Mr Neil Kitchen MD FRCS (SN), and Professor EJ Thompson, PhD MD DSc FRCP FRCPath, for their support and for giving me the opportunity to carry out this work.

Dr Martin Smith FRCA for introducing microdialysis to the Surgical Intensive Care Unit, and for advice, support and encouragement throughout the project.

Mr Antonio Belli MD FRCS FRCS (SN) and Dr Axel Petzold MD PhD, who have given invaluable help, advice and friendship throughout.

Dr Geoff Keir PhD FRCPath FIBMS (Institute of Neurology Department of Neuroinflammation) for much advice, support and assistance in the laboratory.

The Neurosurgical Intensive Care nursing staff for their assistance, in particular for kindly helping to change the microdialysis vials so reliably and for tolerating the inconvenience and extra work imposed by the monitoring.

Dr Hilary Watt for statistical advice.

The patients and their relatives for their selfless participation.

CMA Microdialysis: Mark Dumenil, CEO, Carol Woods, and CMA UK.

Not least, to all of my family. This work is dedicated to them.

Financial Disclosure

Financial Disclosure:

Neither the author, the supervisors, nor the University of London have any financial interest in CMA Microdialysis.

Financial Support:

The Brain Research Trust (Registered Charity No: 263064),

15 Southampton Place,

London WC1A 2AJ.

Telephone: (020) 7404 9982

Thesis Abstract

Introduction: This thesis investigates whether the astrocyte protein S100B is recoverable from brain extracellular fluid (ECF) using intracerebral microdialysis, in patients with acute brain injury (ABI). Previous studies in serum have shown that S100B protein is a predictor of high intracranial pressure and mortality in ABI (Petzold et al 2002). The thesis also examines whether S100B levels correlate with other conventional brain ECF surrogate markers of injury such as lactate, pyruvate, and glutamate. Finally the thesis evaluates the sensitivity of S100B as a predictor of adverse clinical events (such as episodes of raised intracranial pressure, low cerebral perfusion pressure and cerebral vasospasm) and mortality in acute brain injury.

Methods: An in-vitro microdialysis study was carried out to determine S100B protein recovery across the 20kDa cut-off microdialysis catheter (CMA 70). In addition, a prospective, longitudinal study examined 20 patients with ABI (11 traumatic - TBI, and 9 vascular - VBI). Standard 20kDa microdialysis catheters were inserted via burr holes into the peri-lesional region of the brain and recording of microdiaysis on-line tissue chemistry was carried out for as long as deemed clinically appropriate. Brain ECF samples were also collected and stored for laboratory analysis of S100B concentrations using an established ELISA. ICP, CPP and TCD values were also recorded.

Results: S100B was found to be recoverable in-vitro using the 20kDa membrane catheter. Mean recovery was found to be 26.5%. S100B was also recovered from brain ECF microdialysate in-vivo using the same type of catheter. In-vivo concentrations were frequently of much higher value than the mean in-vitro recovery ...