Saunders laboratory: Developmental neuroscience and neurotrauma

Research Overview

Internal environment of the developing brain

This project has two main components:

1. Studies of transfer mechanisms into developing brain (the blood brain and blood-cerebrospinal fluid barriers) demonstrated that tight junctions at these interfaces close off the intercellular transfer even at the earliest stages of brain development. Instead, the transfer appears to be across a small proportion of choroid plexus epithelial cells with uptake into the brain from the CSF, rather than across cerebral blood vessels. Recent studies showed that protein is transferred by different mechanisms but also across a small proportion of choroid plexus cells. The next stage of the work involves molecular characterisation of these transfer mechanisms.

2. Effects of inflammation on brain barriers and brain development. Maternal infection during pregnancy is thought by many obstetricians and paediatricians to be a major cause of brain damage in the newborn. A mechanism of this damage has been suggested to be via an effect of increasing permeability of the blood-brain barrier. Results show that there are substantial differences in blood-brain barrier permeability following induction of an inflammatory response by lipopolysaccharide injection, at different postnatal ages. This may have important implications for brain development in the off-spring of mothers experiencing infections during pregnancy.

Mechanisms of damage and recovery after spinal cord injury

This project is a collaborative one to study the early outgrowth of nerve fibres in the immature spinal cord (opossum) following injury. Elecronmicroscopical and immunocytochemical methods are being used to define changes in the developing spinal cord that may explain the ability of the immature CNS to regenerate, a capacity that is lost later in development. Behavioural studies show correlations between the degree of functional recovery and morphological repair. State of the art molecular techniques will be used to define gene and protein changes.

Traumatic injury to the brain and spinal cord: Limiting the damage

The group is part of a consortium, the Victorian Neurotrauma Research Group, studying the inflammatory response in the early stages of brain and spinal cord injury. The aim is to develop new therapies for limiting secondary brain damage following trauma to the brain or spinal cord.

Staff

Associate Professor Kate Dziegielewska, Principal Research Fellow
Dr Mark Habgood, Senior Research Fellow
Dr C Joakim Ek, Research Fellow
Ms Ann Potter, Research Technician
Dr Shane Liddelow, Research Fellow
Mr Ben Wheaton, Postgraduate Student
Ms Natassya Noor, Postgraduate Student

photo of staff from Developmental Neuroscience and Neurotrauma lab

Collaborators

Prof Kjeld Møllgård, University of Copenhagen
Prof Dalton Dietrich, Director Miami Project
Prof Magdalena Gotz, Director Institute of Stem Cells Research, Munich.
Prof Hans Bauer, University of Salzburg
Dr Hanelore Bauer, University of Salzburg
A/Prof David Christie, Univeristy of Auckland
A/Prof John McDonald, Washington University, St Louis
Prof Klaus Unsicker, University of Heidelberg

Funding

1. NHMRC
2. VTF
3. VNI

Research Publications

  • Ek CJ, Dziegielewska KM, Stolp H, Saunders NR.
    Functional effectiveness of the blood-brain barrier to small water-soluble molecules in developing and adult opossum (Monodelphis domestica).
    J Comp Neurol 2006; 496: 13-26.
  • Johansson PA, Dziegielewska KM, Ek CJ, Habgood MD, Liddelow SA, Potter AM, Stolp HB, Saunders NR.
    Blood-CSF barrier function in the rat embryo.
    Eur J Neurosci 2006; 24: 65-76.
  • Stolp HB, Dziegielewska KM, Ek CJ, Habgood MD, Lane MA, Potter AM, Saunders NR.
    Breakdown of the blood-brain barrier to proteins in white matter of the developing brain following systemic inflammation.
    Cell Tissue Res 2005; 320: 369-78.
  • Stolp HB, Dziegielewska KM, Ek CJ, Potter AM, Saunders NR.
    Long-term changes in blood-brain barrier permeability and white matter following prolonged systemic inflammation in early development in the rat.
    Eur J Neurosci 2005; 22: 2805-16.

Research Projects

This Research Group doesn't currently have any projects



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience, Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact Professor Norman Saunders

Department / Centre

Pharmacology and Therapeutics