Developmental Neuroscience & Neurotrauma Laboratory
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 a 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.
.....................................................
Key References
~EK, C.J., DZIEGIELEWSKA, K.M., STOLP, H. & SAUNDERS, N.R. (2006)
Functional effectiveness of the blood-brain barrier to small water-soluble molecules in developing and adult opossum (Monodelphis domestica).J Comp Neurol, 496, 13-26.
~JOHANSSON, P.A., DZIEGIELEWSKA, K.M., EK, C.J., HABGOOD, M.D., LIDDELOW, S.A., POTTER, A.M., STOLP, H.B. & SAUNDERS, N.R. (2006)
Blood-CSF barrier function in the rat embryo. Eur J Neurosci, 24, 65-76.
~STOLP, H.B., DZIEGIELEWSKA, K.M., EK, C.J., HABGOOD, M.D., LANE, M.A., POTTER, A.M. & SAUNDERS, N.R. (2005)
Breakdown of the blood-brain barrier to proteins in white matter of the developing brain following systemic inflammation.
Cell Tissue Res, 320, 369-78.
~ STOLP, H.B., DZIEGIELEWSKA, K.M., EK, C.J., POTTER, A.M. & SAUNDERS, N.R. (2005)
Long-term changes in blood-brain barrier permeability and white matter following prolonged systemic inflammation in early development in the rat. Eur J Neurosci, 22, 2805-16.
.....................................................