{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T17:00:59Z","timestamp":1787936459502,"version":"build-2784847793"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Neurosurgery Research and Education Foundation (NREF)","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"Neurosurgery Research and Education Foundation (NREF)","award":["1BX004256"],"award-info":[{"award-number":["1BX004256"]}]},{"name":"Neurosurgery Research and Education Foundation (NREF)","award":["1RX001141"],"award-info":[{"award-number":["1RX001141"]}]},{"name":"Neurosurgery Research and Education Foundation (NREF)","award":["T32AI132164"],"award-info":[{"award-number":["T32AI132164"]}]},{"name":"Department of Veterans Affairs","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"Department of Veterans Affairs","award":["1BX004256"],"award-info":[{"award-number":["1BX004256"]}]},{"name":"Department of Veterans Affairs","award":["1RX001141"],"award-info":[{"award-number":["1RX001141"]}]},{"name":"Department of Veterans Affairs","award":["T32AI132164"],"award-info":[{"award-number":["T32AI132164"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["1BX004256"],"award-info":[{"award-number":["1BX004256"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["1RX001141"],"award-info":[{"award-number":["1RX001141"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["T32AI132164"],"award-info":[{"award-number":["T32AI132164"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Germinal matrix hemorrhage (GMH) is a pathology that occurs in infancy, with often devastating long-term consequences. Posthemorrhagic hydrocephalus (PHH) can develop acutely, while periventricular leukomalacia (PVL) is a chronic sequala. There are no pharmacological therapies to treat PHH and PVL. We investigated different aspects of the complement pathway in acute and chronic outcomes after murine neonatal GMH induced at postnatal day 4 (P4). Following GMH-induction, the cytolytic complement membrane attack complex (MAC) colocalized with infiltrating red blood cells (RBCs) acutely but not in animals treated with the complement inhibitor CR2-Crry. Acute MAC deposition on RBCs was associated with heme oxygenase-1 expression and heme and iron deposition, which was reduced with CR2-Crry treatment. Complement inhibition also reduced hydrocephalus and improved survival. Following GMH, there were structural alterations in specific brain regions linked to motor and cognitive functions, and these changes were ameliorated by CR2-Crry, as measured at various timepoints through P90. Astrocytosis was reduced in CR2-Crry-treated animals at chronic, but not acute, timepoints. At P90, myelin basic protein and LAMP-1 colocalized, indicating chronic ongoing phagocytosis of white matter, which was reduced by CR2-Crry treatment. Data indicate acute MAC-mediated iron-related toxicity and inflammation exacerbated the chronic effects of GMH.<\/jats:p>","DOI":"10.3390\/ijms241210171","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T01:31:31Z","timestamp":1686879091000},"page":"10171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Complement Drives Chronic Inflammation and Progressive Hydrocephalus in Murine Neonatal Germinal Matrix Hemorrhage"],"prefix":"10.3390","volume":"24","author":[{"given":"Mohammed","family":"Alshareef","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Children\u2019s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Hatchell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0818-0830","authenticated-orcid":false,"given":"Tyler","family":"Vasas","sequence":"additional","affiliation":[{"name":"College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7622-8106","authenticated-orcid":false,"given":"Khalil","family":"Mallah","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakash","family":"Shingala","sequence":"additional","affiliation":[{"name":"College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cutrone","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, AnMed Health Medical Center, Anderson, SC 29621, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alawieh","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"},{"name":"Ralph Johnson VA Medical Center, Charleston, SC 29401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Eskandari","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1891\/0730-0832.24.3.55","article-title":"Intraventricular hemorrhage in the premature neonate","volume":"24","author":"Owens","year":"2005","journal-title":"Neonatal Netw."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"F37","DOI":"10.1136\/fn.87.1.F37","article-title":"Posthaemorrhagic ventricular dilatation in the premature infant: Natural history and predictors of outcome","volume":"87","author":"Murphy","year":"2002","journal-title":"Arch. 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