α‐Phenyl‐n‐tert‐butyl‐nitrone reduces lipopolysaccharide‐induced white matter injury in the neonatal rat brain

Abstract

Lipopolysaccharide (LPS)-induced white matter injury in the neonatal rat brain is at least partially associated with oxidative stress. alpha-Phenyl-n-tert-butyl-nitrone (PBN) (100 mg/kg) significantly attenuated LPS (1 mg/kg)-induced brain injury, as indicated by the reduction in bilateral ventricular enlargement, apoptotic cell death of oligodendrocytes (OLs), and the loss of OL immunoreactivity in the neonatal rat brain. Protection of PBN was linked with the attenuated oxidative stress induced by LPS, as indicated by the decreased elevation of 8-isoprostane content and by the reduced number of 4-hydroxynonenal or malondialdehyde positive OLs following LPS exposure. Interestingly, while LPS exposure elevated, rather than depleted, levels of the reduced glutathione (GSH) and the GSH/GSSG (oxidized form) ratio, LPS exposure significantly suppressed glutathione peroxidase activity in the rat brain. PBN attenuated LPS-induced alterations in glutathione homeostasis in the rat brain. Additionally, the inflammatory responses were also reduced in the PBN-treated brain, as indicated by the decreased number of activated microglia following LPS exposure and by the consequently decreased elevation of interleukin1-beta and tumor necrosis factor-alpha contents in the rat brain. The overall results suggest that antioxidant PBN, more than a straightforward free radical scavenger, may also involve anti-inflammatory and anti-apoptotic properties in protection of the neonatal rat brain from LPS-induced injury.

Melatonin ameliorates brain injury induced by systemic lipopolysaccharide in neonatal rats

“…In the current study, systemic LPS exposure resulted in nitrosative and oxidative damage similar to that induced by i.c. LPS injection, as reported previously (Fan et al, 2008b, Fan et al, 2008c). Increased expression of NT (Figs.…”

“…Our previous studies have shown that neonatal exposure (postnatal day 5, P5) to lipopolysaccharide (LPS) through an intracerebral (i.c.) injection results in brain inflammation and white matter and neuronal injury in rats, which was closely associated with the increased nitrosative and oxidative stress following LPS exposure (Fan et al, 2008b, Fan et al, 2008c). The inflammatory response that ensues because of the initial occult exogenous oxidative/nitrosative stress becomes a secondary endogenous source of reactive oxygen species (ROS) and reactive nitrogen species (RNS).…”

Role of Recurrent Hypoxia-Ischemia in Preterm White Matter Injury Severity

“…In the clinical setting, other factors may influence the response to rHI that include complex systemic illness, nutritional, metabolic, endocrine, genetic and epigenetic factors. Postnatal infection is an important risk factor for WMI [52]–[54], and a number of inflammatory factors have been shown to cause WMI and promote preOL degeneration [55]–[57]. Recurrent postnatal infections, which may predispose to rHI, are associated with increased risk for progressive WMI in human preterm survivors [58].…”

Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology?

“…However, current data indicate that redox dysregulation contributes to myelination impairment due to early-life inflammation. Alpha-phenyl-n-tert-butyl-nitrone (PBN), a free radical scavenger, protects oligodendrocytes and myelination against neonatal immune challenge (Fan et al, 2008). Likewise, NAC prevents this deficit by attenuating the dysfunction of peroxisomes, organelles important for ROS detoxification and myelin-lipid metabolism (Paintlia et al, 2008).…”