UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
Web: http://events.um.edu.mt/scisem/
Email: scisem@um.edu.mt
Abstract form
Title: Excitotoxic white matter injury - studies from cell culture and brain
slice models
Presenter: Dr. Mario Valentino Ph.D
Contact address: Department of Physiology & Biochemistry, University of Malta,
Msida MSD 2080
Tel: 2340-2775
Fax: 21 310577
Email: valentino.mario@gmail.com
Presentation date: 22nd October 2007
Abstract
Although the pathophysiology of neuronal death in cerebral ischemia has been intensively
studied, much less attention has focused on ischemic white matter (WM) damage. Because
focal cerebral ischemia in humans damages both gray and WM, an understanding of WM
injury is important in devising potential therapeutic approaches.
An important limitation for studies of cerebral hypoxia-ischemia has been the lack of
experimental models and research tools optimized for WM injury. Current in vitro systems
utilize short-term preparations of optic nerve, peripheral nerve or spinal cord – these are
important pure white matter tracts but not most commonly affected by stroke. For our
studies of cerebral white matter injury we have developed two novel models which allow
detailed examination of axon structure, function, and cell-cell interactions: a culture model
of isolated axons and axons/oligodendrocytes and a brain slice model of myelinated axons
within the mature corpus callosum (http://www.scisys.info/.)
In addition, we have
developed validated electrophysiological and morphological assessment methods with
parallel results obtained from visualization of YFP expression in transgenic mice,
immunocytochemical markers, and electron microscopy (Glia 50:321-328., 2005.,
J.Neuroscience, 27(15) 4420-4229.,2007).
Our results in cell culture and brain slice show that cortical axons are vulnerable to
hypoxic-ischemic injury initiated by activation of voltage-gated sodium channels and
requiring the presence of extracellular calcium. In addition, we identified a role for
AMPA/KA glutamate receptor activation, most likely by free radical-mediated toxicity on
oligodendrocytes with indirect effects on axons. These results agree with those obtained in
isolated optic nerve and spinal cord models and are consistent in identifying the earliest steps
in disruption of ion homeostasis and electrical conduction loss.
Recommended bibliography
McCarran WJ, Goldberg MP. White matter axon vulnerability to AMPA/kainate receptor-mediated ischemic
injury is developmentally regulated. J Neurosci. 2007;27(15):4220-9.
Ness JK, Valentino M, McIver SR, Goldberg MP. Identification of oligodendrocytes in experimental disease
models. Glia. 2005;50(4):321-8.