Ethyl pyruvate protects against lipopolysaccharide-induced white matter injury in the developing rat brain

Abstract

The neuroprotective effects of ethyl pyruvate (EP) have been proved in several brain injury models, yet very little is known about its action on neonatal white matter injury. To investigate the effect of EP on white matte damage, a stereotactic intracerebral injection of lipopolysaccharide (LPS, 1mg/kg) was performed on postnatal day 5 Sprague-Dawley rat pups, and EP was administrated intraperitoneally at a dose of 40mg/kg immediately, 1h and 12h after LPS exposure. Significantly, treatment with EP reduced LPS-induced ventricle dilation, loss of O4+ and O1+ oligodendrocytes, apoptosis of oligodendrocytes, and hypomyelination. The protective effect of EP was associated with suppressed inflammatory responses, indicated by the inhibition of activation of microglia and astrocytes, as well as the decreased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in rat brains. Also, EP prevented the elevation of cleaved caspase-3 in periventricular white matter tissue after LPS insult. Taken together, these results suggest that EP confers potent protection against LPS-induced white matter injury via its anti-inflammatory and anti-apoptotic properties.