The role of neural interleukin-1 beta during healing and repair in the perinatal brain of the mouse
Description
The roles of interleukin-1$\beta$ (IL-1$\beta$) after prenatal trauma in the perinatal brain were studied by lesioning fetal mice in utero at embryonic day 18 (E18) and examining them at postnatal days zero and six (P0 and P6), corresponding to 2 and 9 days postlesion, respectively The regulation of glia limitans reformation by IL-1$\beta$ following neural trauma in the prenatal mouse brain was examined by immunocytochemistry and computer-assisted image analysis. Studies using the human recombinant IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of the IL-1 neural receptor, revealed that IL-1$\beta$ binding to neural IL-1 receptors was necessary for astrocytes to form the new glia limitans that ultimately closed off exposed neural tissue Significantly increased IL-1$\beta$ immunoreactivity was measured in vehicle-injected or nontreated prenatally lesioned animals at the lesion site and in neural parenchyma near the lesion. IL-1$\beta$ immunoreactivity significantly decreased in animals treated with IL-1ra. Both human recombinant IL-1$\beta$ and IL-1ra + IL-1$\beta$ combination injections restored IL-1$\beta$ immunoreactivity upregulation in perilesional tissue Upregulation of IL-1$\beta$ immunoreactivity was due, at least in part, to local IL-1$\beta$ mRNA production, as shown by in situ hybridization. IL-1$\beta$ mRNA was significantly upregulated in cells of varying morphologies near the lesion site. IL-1ra and IL-1$\beta$ injections significantly increased IL-1$\beta$ mRNA in cells near the lesion site as compared to vehicle-injected animals. When IL-1ra and IL-1$\beta$ were injected simultaneously, IL-1$\beta$ mRNA levels were not significantly different from vehicle-injected animals Finally, the role IL-1$\beta$ might play in cell death following traumatic perinatal brain injury was examined. Animals treated with IL-1ra showed significantly increased areas of total cell death and apoptosis when compared to vehicle. In contrast, animals treated with IL-1$\beta$ showed significantly decreased areas of total cell death and apoptosis as compared to IL-1ra-treated animals. The addition of IL-1$\beta$ to IL-1ra treatment at the time of injection attenuated the increase in both types of cell death induced in IL-1ra-treated animals Viewed together, these studies provide evidence that IL-1$\beta$ binding to the neural IL-1 receptor is an important signal to activate cellular survival and activity culminating in successful healing and repair in the damaged perinatal mouse brain