Disturbed maturation of oligodendrocyte progenitors in lipopolysaccharide-induced hypomyelination in cultured forebrain slices of neonatal rats

Introduction
This study was performed to determine whether the disturbed maturation of oligodendrocyte (OL) progenitors might be related to lipopolysaccharide (LPS)-induced hypomyelination.

Material and methods
We created organotypic cultures of forebrain slices from neonatal rats and explored the morphological changes of glial cells expressing tumour necrosis factor  (TNF-) following LPS exposure.

Results
We observed marked activation of glial fibrillary acidic protein-positive astrocytes and OX42-positive microglia co-labelled with TNF- four days following LPS exposure. Our results further demonstrated a reduced expression of O4-positive and O1-positive OL progenitors; moreover, we found that their morphologies were suggestive of degeneration (e.g., scanty, rounded bodies with short, fragmented processes and/or cytoplasmic condensation). At seven days following LPS exposure, astrocytes and microglia were still co-labelled for TNF-; however, the expression of O4-positive and O1-positive cells somewhat increased compared to the number observed at 4 days; despite remaining undifferentiated and exhibiting immature morphologies, the cells were likely indicative of regeneration. In contrast, O4-positive and O1-positive cells in controls were well-differentiated, displaying round, thick cell bodies and long, branching processes.

Conclusions
In conclusion, maturation arrest and/or under-differentiation of OL progenitors commonly occur during regeneration: they may underlie the degeneration and consequent hypomyelination occurring late after injury, or apoptosis during the acute stage post-injury. Microglia and astrocytes expressing TNF- may also contribute to later myelination failure.