Astrocyte and oligodendrocyte damage early before demyelination

Epub: Zhang F, Yao SY, Whetsell WO Jr, Sriram S. Astrogliopathy and oligodendrogliopathy are early events in CNS demyelination. Glia. 2013 Jul 5. doi: 10.1002/glia.22513. 

We examined the phenotypic composition of cells and the underlying mechanisms of demyelination following injection of lipopolysaccharide (LPS) into the corpus callosum (the neural road between the left and right sides of the brain) of rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed fragmented DNA (damaged DNA), which co-localized with oligodendrocytes in areas of demyelination following intracerebral injection with LPS. Immunostaining showed the presence of caspase 3 in cells which expressed the oligodendrocyte markers, suggesting activation of the apoptotic (cell suicide) pathway. Commensurate reduction in glial fibrillary acid protein (GFAP)+/ gap junction protein connexin43+ (Cx43) cells, was also seen in the corpus callosum prior to histochemical evidence of demyelination. Expression of mRNA for proinflammatory cytokines was maximal 3 day post-injection, at a time when the numbers of TUNEL positive cells in the corpus callosum were declining and the total number of CD68+ cells (macrophages) peaked at day 14 post-injection. Our studies suggest that death of oligodendrocytes is an early event in LPS model of demyelination. We believe that the innate immune model of oligodendrocyte death will be useful in the development of neuroprotective agents capable of rescuing oligodendrocytes from apoptosis.


LPS is a sugar molecule from bacteria that stimulates an inflammatory response. If injected in the brain it can cause demyelination. That damage to oligodendrocytes in demyelination is hardly surprising. This study shows early damage to astrocytes. For many years these cells have been ignored. However they are vital to maintain the health of the nervous system. Does the astrocyte damage play a role in demyelination? It is had to say but this maybe a new tool for looking at things to modify demyelination. 

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