ASTROGLIAL RESPONSE IN A CONTEXT OF BRAIN EDEMA USING AN EXPERIMENTAL MODEL OF “COLD-INJURY”

FRISCHKNECHT E; VIDOS C; RAMOS AJ; VILLARREAL A

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2024

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

Astrocytes respond to Brain injury through a process of reactiveastrogliosis increasing in size and morphological complexity, losinghomeostatic functions and showing transcriptional changes. Reactiveastrogliosis is a progressive phenomenon and can achievetime-stable phenotypic changes. Brain edema, which is an increasein interstitial water content, is an early event after many differentbrain injuries and pathologies. We hypothesize that transcriptomicchanges underlying astrocyte reactive phenotypes in a context ofbrain edema are regulated by epigenetic mechanisms of histoneposttranslational modifications. We here aimed to characterize astrocyteresponse in a model of cold injury. Such a paradigm of brainedema is promoted by localized cold exposure of only one brainhemisphere without direct physical disruption of neither skull, meningesnor nerve tissue. We conducted our studies in adult femaleand male mice (C57/4-5 months). The “non-exposed” (contralateral)hemisphere was used as an immunoreactivity base-line for comparisons.Using immunofluorescent co-labeling followed by epifluorescenceand confocal microscopy we addressed immunoreactivityfor astrocyte marker GFAP (glial fibrillary acidic protein), AQP4(aquaporin 4) and C3 (complement 3). Our results showed an increasein GFAP immunoreactivity at 1DPL (days post lesion) whichremained for 3 and 7 DPL. AQP4 immunoreactivity showed only tobe increased at 1DPL. We further observed an increase in C3 immunoreactivitybut, interestingly, with no colocalization with GFAP.We conclude from this preliminary work that the cold-injury model ofbrain edema promotes a progressive astroglial response and resultssuitable for addressing epigenetic changes in reactive astrocytes atdifferent time points of reactive astrogliosis. It is of note that thismodel will allow addressing cellular response in a context of brainedema, a pathological condition of high clinical relevance.