title: Global hypomethylation defines a sub-population of reactive microglia/macrophages in experimental traumatic brain injury.
abstract: Global alterations in gene expression have been observed in different traumatic brain injury (TBI) models and are considered of crucial importance to the development of subsequent tissue injury and repair. Cytosine methylation is a well-known process of endogenous DNA modification in mammals and the primary mechanism responsible for changes in epigenetic gene expression. Here we have investigated the early global spatio-temporal changes of the status of cellular DNA methylation in a rat TBI model by immunohistochemistry and analyzed the effects of dexamethasone on these changes. Global cellular hypomethylation was seen as early as day 1 in pannecrosis and day 2 in peripannecrosis following TBI. A sub-population of reactive microglia/macrophages was identified as the major source of hypomethylated cells by double-staining experiments. Further, peripheral administration of dexamethasone suppressed this lesional hypomethylation at day 2 post-injury. In sum, our data suggest that lesional hypomethylation defines a sub-population of activated microglia/macrophages involved in the early processes following traumatic brain injury.
authors.affiliation: Institute of Brain Research, University of Tuebingen, Calwer Street 3, D-72076 Tuebingen, Germany.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Zhang
authors.forename: Uwe
authors.initials: U
authors.lastname: Fauser
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Schluesener
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D019175:DNA Methylation; D003907:Dexamethasone; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000502:physiology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013997:Time Factors
chemical_list: D003907:Dexamethasone