{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:42:45Z","timestamp":1775806965931,"version":"3.50.1"},"reference-count":77,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,6,27]],"date-time":"2011-06-27T00:00:00Z","timestamp":1309132800000},"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":[[2011,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective:<\/jats:title><jats:p>Inflammation promotes epidermal wound healing but is considered detrimental to recovery from central nervous system injury. Sick infants have increased levels of cytokines in their cerebrospinal fluid that correlate with poor neurological outcome. In this study, we investigated the role of neuroinflammation and more specifically interleukin 6 (IL\u20106) in the amplification of subventricular zone (SVZ) and subgranular zone (SGZ) neural precursors after neonatal brain injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Neonatal hypoxia\/ischemia (H\/I) was induced in P6 rat pups, and IL\u20106 was quantified with or without indomethacin administration. Neural precursor responses were evaluated by neurosphere assays as well as by stereological analyses. Studies were performed to determine how IL\u20106 and leukemia\u2010inhibiting factor (LIF) affect SVZ cell expansion, proliferation, and self\u2010renewal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Consistent with earlier studies, medially situated SVZ cells expanded after H\/I. Contrary to our expectations, indomethacin significantly decreased both the initial reactive increase in these precursors and their ability to self\u2010renew. By contrast, indomethacin increased proliferation in the SGZ and lateral SVZ. Indomethacin diminished the accumulation of microglia\/macrophages and IL\u20106 production after H\/I. In vitro IL\u20106 enhanced neurosphere growth, self\u2010renewal, and tripotentiality and was more effective than LIF in promoting self\u2010renewal. Enhanced precursor self\u2010renewal also was obtained using prostaglandin E2, which is downstream of cyclooxygenase 2 and a target of indomethacin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation:<\/jats:title><jats:p>These data implicate neuroinflammation and in particular IL\u20106 as a positive effector of primitive neural precursor expansion after neonatal brain injury. These findings have important clinical implications, as indomethacin and other anti\u2010inflammatory agents are administered to premature infants for a variety of reasons. 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