Glial response to brain cold injury in mice, an animal model of edema

Glial cells including astrocytes and microglia coordinately respond to brain injuries and are promising targets to modulate damage propagation. Using an edema model by cold injury in young adult female and male mice (C57/4-5 months), we aimed to describe astrocyte and microglia responses at 1-, 3- and 7-days post lesion (DPL). We used qPCR to address mRNA levels of specific genes and immunofluorescent colabeling followed by epifluorescence and confocal microscopy to study immunoreactivity for different glial and neuronal markers. We observed a progressive increase in GFAP (glial fibrillary acidic protein) immunoreactivity and a transient increase in AQP4 (aquaporin 4) immunoreactivity at 1DPL. IBA1 (Ionized calcium-binding adaptor molecule 1) immunoreactivity progressively increased at 1, 3 and 7DPL while NeuN (neuronal nuclear protein) radically decreased around the injury core. Interestingly we observed an increase in C3 (complement 3) immunoreactivity which did not colocalize with any of the markers mentioned. C3 strongly colocalized with mouse IgG, probably suggesting an entrance from peripheral blood. We conclude that this model of brain edema promotes a progressive astroglial response concomitantly with neuronal stress, being suitable for addressing molecular (epigenetic) changes in reactive glial cells at different time points of reactive astrogliosis. Recent preliminary results from our group showed changes in mRNA expression of microglial genes and C3 receptor alpha.