{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T01:58:09Z","timestamp":1793843889107,"version":"4.6.1"},"reference-count":31,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>Neutrophils are the most abundant leukocytes and usually the first immune cell-type recruited to a site of infection or tissue damage. In asphyxiated neonates, elevated peripheral neutrophil counts are associated with poorer neurological outcomes. Induced neutropenia provides brain protection in animal models of neonatal hypoxic-ischemic (HI) injury, but the anti-neutrophil serum used in past studies heavily cross-reacts with monocytes, thus complicating the interpretation of results. Here we examined neutrophil influx and extravasation, and used a specific anti-Ly6G antibody for induced neutropenia against lipopolysaccharide (LPS)-pretreated HI injury in murine neonates, a model for inflammation-sensitized hypoxic-ischemic encephalopathy (HIE). As early as 6\u2009h after the LPS\/HI insult, the mRNAs for neutrophil-recruiting and mitogenic chemokines ascended in the ipsilateral hemisphere, coinciding with immuno-detection of neutrophils. However, neutrophils mainly resided within blood vessels, exhibiting signs for neutrophil extracellular traps (NETs), before 48\u2009h post-LPS\/HI. Prophylactic anti-Ly6G treatment blocked the brain infiltration of neutrophils, but not monocytes or lymphocytes, and markedly decreased LPS\/HI-induced pro-inflammatory cytokines, matrix metalloproteinase 9 (MMP-9), and brain tissue loss. In contrast, anti-Ly6G treatment at 4\u2009h post-LPS\/HI failed to prevent the influx of neutrophils and brain damage. Together, these results suggest important pathological functions for early-arriving neutrophils in inflammation-sensitized HIE.<\/jats:p>","DOI":"10.1177\/0271678x19891839","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T23:56:36Z","timestamp":1576540596000},"page":"2188-2200","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":48,"title":["Early neutrophil infiltration is critical for inflammation-sensitized hypoxic-ischemic brain injury in newborns"],"prefix":"10.1177","volume":"40","author":[{"given":"Hui-Wen","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Neuroscience and the Center for Brain Immunology and Glia (BIG), University of Virginia School of Medicine, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yi","family":"Kuan","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and the Center for Brain Immunology and Glia (BIG), University of Virginia School of Medicine, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"key":"bibr1-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.13"},{"key":"bibr2-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.08.024"},{"key":"bibr3-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.20.2677"},{"key":"bibr4-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2013.12.006"},{"key":"bibr5-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2582-14.2014"},{"key":"bibr6-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2017.10.006"},{"key":"bibr7-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.45"},{"key":"bibr8-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1381-0"},{"key":"bibr9-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1126\/science.1195491"},{"key":"bibr10-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam8897"},{"key":"bibr11-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.06.006"},{"key":"bibr12-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.105"},{"key":"bibr13-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12352"},{"key":"bibr14-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.07.070"},{"key":"bibr15-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200409"},{"key":"bibr16-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2980-15.2015"},{"key":"bibr17-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jp.7211750"},{"key":"bibr18-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V76.12.2613.2613"},{"key":"bibr19-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199705000-00002"},{"key":"bibr20-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199904010-00008"},{"key":"bibr21-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000113546.03897.FC"},{"key":"bibr22-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.05.024"},{"key":"bibr23-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2753-2"},{"key":"bibr24-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0407247"},{"key":"bibr25-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0113014"},{"key":"bibr26-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1232221"},{"key":"bibr27-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2015.02.034"},{"key":"bibr28-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-844530"},{"key":"bibr29-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.06.017"},{"key":"bibr30-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002470"},{"key":"bibr31-0271678X19891839","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000092527.33910.89"}],"container-title":["Journal of Cerebral Blood Flow &amp; 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