Expression and role of Galectins 1 and 3 in the lesioned brain

Astrocytes react to brain injury in a heterogeneous manner with only a subset resuming proliferation and acquiring in vitro neural stem cell properties. In order to identify novel regulators of this astrocyte subset, we performed a genome-wide expression analysis of reactive astrocytes isolated 5 days after stab wound injury from the adult mouse cerebral cortex. The expression pattern was compared with astrocytes from normal cortex and adult neural stem cells isolated from the sub-ependymal zone (GSE18765). These comparisons revealed a set of genes up-regulated both in neurogenic neural stem cells and reactive astrocytes, including the lectins Galectin-1 and -3. These results, as well as the pattern of Galectin expression in the lesioned brain, led us to examine the functional significance of these lectins in brains of Galectin-1/3 double-knockout mice. Following stab wound injury, astrocyte reactivity, proliferation and neurosphere formation were all found to be significantly reduced in the absence of Galectin-1/3. This phenotype could be recapitulated in vitro and was fully rescued by addition of Galectin-3, but not of Galectin-1. Staining of sections obtained from patients suffering from cavernoma further underline the significance of Galectin-3 expression in reactive astrocytes. We performed gene expression microarray analysis on reactive and non-reactive astrocytes from mouse cortical tissue.