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Maternal inflammation/infection alone or in combination with birth asphyxia increases the risk for perinatal brain injury. Free radicals are implicated as major mediators of inflammation and hypoxia‐ischemia (HI)–induced perinatal brain injury. This study evaluated the neuroprotective efficacy of a scavenging agent, N‐acetylcysteine (NAC), in a clinically relevant model.Lipopolysaccharide (LPS)‐sensitized HI brain injury was induced in 8‐day‐old neonatal rats. NAC was administered in multiple doses, and brain injury was evaluated at 7 days after HI.NAC (200mg/kg) provided marked neuroprotection with up to 78% reduction of brain injury in the preꚋ‐HI treatment group and 41% in the early (0 hour) post‐HI treatment group, which was much more pronounced protection than another free radical scavenger, melatonin. Protection by NAC was associated with the following factors: (1) reduced isoprostane activation and nitrotyrosine formation; (2) increased levels of the antioxidants glutathione, thioredoxin‐2, and (3) inhibition of caspase‐3, calpain, and caspase‐1 activation.NAC provides substantial neuroprotection against brain injury in a model that combines infection/inflammation and HI. Protection by NAC was associated with improvement of the redox state and inhibition of apoptosis, suggesting that these events play critical roles in the development of lipopolysaccharide‐sensitized HI brain injury. Ann Neurol 2007 [ABSTRACT FROM AUTHOR]

Objective: To examine fetal brain injury in the Göttingen minipig following intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational length.Methods: We performed laparotomy after anesthesia in six pregnant sows. We randomized 29 fetuses to one of four groups: pretreatment with saline or endotoxin followed by 30 min of umbilical cord occlusion or no occlusion. After 48 h we performed a re-laparotomy and examined the fetal brains.Results: After total asphyxia, brain stem injury was present in the group pretreated with saline (P<0.01 vs. controls) and with endotoxin (P<0.005 vs. controls). Microglia activation was more marked in the brain stem (P<0.05) and posterior white matter (P<0.05) in the asphyxia group than in controls. Two of five fetuses in the asphyxia group had white matter injury, while no white matter lesions were found in the asphyxia/inflammation or endotoxin only groups.Conclusions: In this Göttingen minipig model, a species closer to humans than animals commonly used in experimental studies of perinatal brain injuries, intrauterine asphyxia following pretreatment with saline caused brain stem and white matter injury. This model can be further developed to study the impact of other intrauterine exposures on brain injury. [ABSTRACT FROM AUTHOR]