Suppression of glial activation is involved in the protection of IL-10 on maternal E. coli induced neonatal white matter injury

Abstract

White matter damage (WMD) is an important cause of disability including cerebral palsy in preterm, low birth-weight infants. Maternal infection is now recognized as one of the risk factors for WMD. Previously we reported that intrauterine inoculation of Escherichia coli to pregnant rats resulted in WMD in offspring and interleukin-10 (IL-10) was protective against this damage. The objective of this study was to elucidate the mechanism involved in the protective effect of IL-10 against neonatal WMD. We found that E. coli treatment in dams resulted in significant apoptosis in periventricular white matter of rat pups on postnatal day 0 (P0). On P8, a remarkable increase in ED-1 immunostaining (indicating either microglial activation or macrophage infiltration) was detected in brains of pups in the E. coli-treated group. Astrogliosis was also noticed in brain white matter of pups in the E. coli-treated group. In addition to the strong activation of microglia and astrocytes, oligodendrocytes (OLs) were significantly reduced in periventricular areas in the brains of pups from the E. coli-treated group. Later, on P15, hypomyelination was also noticed in rat brains from the E. coli-treated group, using myelin basic protein (MBP) immunostaining. Treatment with IL-10 after E. coli inoculation significantly reduced TUNEL staining and caspase-3 activation, and partially restored the impaired immunostaining markers for immature and mature OLs, such as CNPase, O4, adenomatous polyposis coli (APC) and MBP. These results indicate that the protective effect of IL-10 against brain WMD is linked with suppression of microglial activation/macrophage infiltration, as shown by significantly reduced ED-1+ cells in the white matter.