Brain keratan sulfate and glial scar formation

In response to injury to the central nervous system (CNS), reactive astrocytes appear and accumulate in the wounded area, leading to glial scar formation. Glial scar is the physical barrier to axonal regeneration of injured neurons. Chondroitin sulfate proteoglycans are inhibitory to axon outgrowth and are upregulated in reactive astrocytes upon CNS injury. It is known that keratan sulfate proteoglycans (KSPGs) are also augmented after CNS injury and act as inhibitory cues. We give a brief overview of CNS injury and cover our recent data regarding the relationship between glial scar formation and KS. KS expression in the developing brain is detectable with 5D4, a KS-specific monoclonal antibody. These 5D4 immunoreactivities are eliminated in mice deficient in N-acetylglucosamine 6-O-sulfotransferase-1. In adult mice, brain injury apparently upregulates mRNA expression of N-acetylglucosamine 6-O-sulfotransferase-1 as well as 5D4-reactive KS in the wounded area. Intriguingly, the expression of 5D4-reactive KS and reactive astrocyte accumulation in the wounded area are dramatically diminished in the sulfotransferase-deficient mice. Consequently, the deficient mice exhibit a marked reduction in scar formation and enhancement of neuronal regeneration after brain injury. Thus, N-acetylglucosamine 6-O-sulfotransferase-1 plays indispensable roles in brain KS biosynthesis and glial scar formation after brain injury.