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It is known that activation of an innate immune response is a key, contributing factor in perinatal brain injury; therefore, the neuroprotective therapeutic potential of innate defense regulator peptides (IDRs) was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The anti\u2010inflammatory effects of 3 IDRs was measured in lipopolysaccharide (LPS)\u2010activated murine microglia. IDRs were then assessed for their ability to confer neuroprotection in vivo when given 3 hours after neonatal brain injury in a clinically relevant model that combines an inflammatory challenge (LPS) with hypoxia\u2013ischemia (HI). To gain insight into peptide\u2010mediated effects on LPS\u2010induced inflammation and neuroprotective mechanisms, global cerebral gene expression patterns were analyzed in pups that were treated with IDR\u20101018 either 4 hours before LPS or 3 hours after LPS+HI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IDR\u20101018 reduced inflammatory mediators produced by LPS\u2010stimulated microglia cells in vitro and modulated LPS\u2010induced neuroinflammation in vivo. When administered 3 hours after LPS+HI, IDR\u20101018 exerted effects on regulatory molecules of apoptotic (for, eg, Fadd and Tnfsf9) and inflammatory (for, eg, interleukin 1, tumor necrosis factor \u03b1, chemokines, and cell adhesion molecules) pathways and showed marked protection of both white and gray brain matter.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>IDR\u20101018 suppresses proinflammatory mediators and cell injurious mechanisms in the developing brain, and postinsult treatment is efficacious in reducing LPS\u2010induced hypoxic\u2013ischemic brain damage. IDR\u20101018 is effective in the brain when given systemically, confers neuroprotection of both gray and white matter, and lacks significant effects on the brain under normal conditions. Thus, this peptide provides the features of a promising neuroprotective agent in newborns with brain injury. ANN NEUROL 2014;75:395\u2013410<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24087","type":"journal-article","created":{"date-parts":[[2013,12,13]],"date-time":"2013-12-13T21:28:38Z","timestamp":1386970118000},"page":"395-410","source":"Crossref","is-referenced-by-count":64,"title":["Innate defense regulator peptide 1018 protects against perinatal brain injury"],"prefix":"10.1002","volume":"75","author":[{"given":"Hayde","family":"Bolouri","sequence":"first","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Physiology, Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"S\u00e4vman","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Physiology, Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden"},{"name":"Department of Pediatrics, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Physiology, Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anitha","family":"Thomas","sequence":"additional","affiliation":[{"name":"Centre for Drug Research and Development Vancouver, British Columbia  Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Maurer","sequence":"additional","affiliation":[{"name":"Centre for Drug Research and Development Vancouver, British Columbia  Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edie","family":"Dullaghan","sequence":"additional","affiliation":[{"name":"Centre for Drug Research and Development Vancouver, British Columbia  Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Fjell","sequence":"additional","affiliation":[{"name":"James Hogg Research Centre University of British Columbia at St Paul's Hospital Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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