Regulation by Interleukin-1β of Formation of a Line of Delimiting Astrocytes Following Prenatal Trauma to the Brain of the Mouse

The regulation of perinatal glia limitans (GL) reformation by interleukin-1β (IL-1β) following prenatal neural trauma in the mouse was studied in lesioned fetal mice by immunocytochemistry and computer-assisted image analysis for presence and distribution of astrocytes and IL-1β immunoreactivity (ir). Astrocytes stained with anti-glial fibrillary acidic protein (GFAP) were observed as a line of delimiting astrocytes (LDA) near the lesion edge on Postnatal Day 0 (P0, 2 days postlesion). At P6, a new and complete GL composed of GFAP-positive astrocytes was continuous with that of adjacent undamaged tissue. The new GL was located in the same area at P6 as was the LDA at P0, suggesting that the LDA is the precursor structure to a reformed GL. Astrocytes comprising the new GL were positive for anti-IL-1β. The IL-1 receptor antagonist (IL-1ra), administered acutely into the lesion, produced a significantly decreased optical density of IL-1β-ir at the LDA at P0 compared to animals that received injections of vehicle, human recombinant IL-1β, or a combination injection of IL-1ra + IL-1β. Furthermore, although GFAP-stained cells appeared at the lesion site, an organized LDA was not visible at P0 in IL-1ra-treated animals. Vehicle-, IL-1β-, and combination-injected animals showed a robust LDA at the lesion site at P0. These data suggest that upregulation of IL-1β in astrocytes and interaction of IL-1β with the neural IL-1 receptor are important for reconstruction of the GL following prenatal lesion in the murine brain.