{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T14:35:54Z","timestamp":1782830154331,"version":"3.54.5"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,1,25]],"date-time":"2007-01-25T00:00:00Z","timestamp":1169683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>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\u2010ischemia (HI)\u2013induced perinatal brain injury. This study evaluated the neuroprotective efficacy of a scavenging agent, <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC), in a clinically relevant model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lipopolysaccharide (LPS)\u2010sensitized HI brain injury was induced in 8\u2010day\u2010old neonatal rats. NAC was administered in multiple doses, and brain injury was evaluated at 7 days after HI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NAC (200mg\/kg) provided marked neuroprotection with up to 78% reduction of brain injury in the pre+post\u2010HI treatment group and 41% in the early (0 hour) post\u2010HI 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\u20102, and (3) inhibition of caspase\u20103, calpain, and caspase\u20101 activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>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\u2010sensitized HI brain injury. 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