{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:08:16Z","timestamp":1791216496718,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2016,4,2]],"date-time":"2016-04-02T00:00:00Z","timestamp":1459555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes including vasospasm, cognitive decline, and even death. Currently, treatment options are limited for this potentially life threatening injury. Recent evidence suggests that neuroinflammation plays a critical role in injury expansion and brain damage. Red blood cell breakdown products can lead to the release of inflammatory cytokines that trigger vasospasm and tissue injury. Preclinical models have been used successfully to improve understanding about neuroinflammation following aneurysmal rupture. The focus of this review is to provide an overview of how neuroinflammation relates to secondary outcomes such as vasospasm after aneurysmal rupture and to critically discuss pharmaceutical agents that warrant further investigation for the treatment of subarachnoid hemorrhage. We provide a concise overview of the neuroinflammatory pathways that are upregulated following aneurysmal rupture and how these pathways correlate to long-term outcomes. Treatment of aneurysm rupture is limited and few pharmaceutical drugs are available. Through improved understanding of biochemical mechanisms of injury, novel treatment solutions are being developed that target neuroinflammation. In the final sections of this review, we highlight a few of these novel treatment approaches and emphasize why targeting neuroinflammation following aneurysmal subarachnoid hemorrhage may improve patient care. We encourage ongoing research into the pathophysiology of aneurysmal subarachnoid hemorrhage, especially in regards to neuroinflammatory cascades and the translation to randomized clinical trials.<\/jats:p>","DOI":"10.3390\/ijms17040497","type":"journal-article","created":{"date-parts":[[2016,4,4]],"date-time":"2016-04-04T10:44:35Z","timestamp":1459766675000},"page":"497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":276,"title":["Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-4080","authenticated-orcid":false,"given":"Brandon","family":"Lucke-Wold","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aric","family":"Logsdon","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branavan","family":"Manoranjan","sequence":"additional","affiliation":[{"name":"McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-0645","authenticated-orcid":false,"given":"Ryan","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-8019","authenticated-orcid":false,"given":"Evan","family":"McConnell","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Vates","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Simard","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery, Pathology, and Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"384342","DOI":"10.1155\/2014\/384342","article-title":"Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage","volume":"2014","author":"Miller","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jns.2013.07.004","article-title":"Erythropoietin prevents delayed hemodynamic dysfunction after subarachnoid hemorrhage in a randomized controlled experimental setting","volume":"332","author":"Guresir","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4973","DOI":"10.3390\/ijms16034973","article-title":"Glibenclamide for the treatment of ischemic and hemorrhagic stroke","volume":"16","author":"Caffes","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1161\/STROKEAHA.112.659821","article-title":"Pharmacological stabilization of intracranial aneurysms in mice: A feasibility study","volume":"43","author":"Makino","year":"2012","journal-title":"Stroke"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s40064-015-0970-2","article-title":"Immune cells subpopulations in cerebrospinal fluid and peripheral blood of patients with aneurysmal subarachnoid hemorrhage","volume":"4","author":"Moraes","year":"2015","journal-title":"SpringerPlus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1742-2094-11-2","article-title":"The rodent endovascular puncture model of subarachnoid hemorrhage: Mechanisms of brain damage and therapeutic strategies","volume":"11","author":"Kooijman","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5028","DOI":"10.3390\/ijms16035028","article-title":"Methemoglobin is an endogenous toll-like receptor 4 ligand-relevance to subarachnoid hemorrhage","volume":"16","author":"Kwon","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S177","DOI":"10.1007\/s12028-014-0038-0","article-title":"Participants in the International Multi-disciplinary Consensus Conference on Multimodality, M. Monitoring inflammation (including fever) in acute brain injury","volume":"21","author":"Provencio","year":"2014","journal-title":"Neurocrit. Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.brainres.2014.08.036","article-title":"Pharmacologic blockade of vascular adhesion protein-1 lessens neurologic dysfunction in rats subjected to subarachnoid hemorrhage","volume":"1586","author":"Xu","year":"2014","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1227\/00006123-198001000-00001","article-title":"Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning","volume":"6","author":"Fisher","year":"1980","journal-title":"Neurosurgery"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1161\/01.STR.19.10.1250","article-title":"Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage","volume":"19","author":"Hijdra","year":"1988","journal-title":"Stroke J. Cereb. Circ."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.nec.2009.10.008","article-title":"Inflammation and cerebral vasospasm after subarachnoid hemorrhage","volume":"21","author":"Pradilla","year":"2010","journal-title":"Neurosurg. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1080\/15216540500380871","article-title":"Hemoglobin and heme scavenging","volume":"57","author":"Ascenzi","year":"2005","journal-title":"IUBMB Life"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2176\/nmc.30.10","article-title":"Red blood cells are essential for late vasospasm following experimentally induced subarachnoid hemorrhage in dogs","volume":"30","author":"Nozaki","year":"1990","journal-title":"Neurol. Medico Chir."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.lfs.2004.02.010","article-title":"Time course of production of hydroxyl free radical after subarachnoid hemorrhage in dogs","volume":"75","author":"Macdonald","year":"2004","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/(SICI)1098-1063(1997)7:3<341::AID-HIPO8>3.0.CO;2-N","article-title":"Adhesion molecule expression on phagocytic microglial cells following anterograde degeneration of perforant path axons","volume":"7","author":"Hailer","year":"1997","journal-title":"Hippocampus"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1179\/016164106X152025","article-title":"Leukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage","volume":"28","author":"Gallia","year":"2006","journal-title":"Neurol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/00006123-200003000-00001","article-title":"Molecular keys to the problems of cerebral vasospasm","volume":"46","author":"Dietrich","year":"2000","journal-title":"Neurosurgery"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1097\/00006123-198611000-00008","article-title":"Serum immunocomplexes in patients with subarachnoid hemorrhage","volume":"19","author":"Pellettieri","year":"1986","journal-title":"Neurosurgery"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"741","DOI":"10.3171\/jns.1989.71.5.0741","article-title":"Activated complement components C3a and C4a in cerebrospinal fluid and plasma following subarachnoid hemorrhage","volume":"71","author":"Kasuya","year":"1989","journal-title":"J. Neurosurg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1254\/jjp.88.227","article-title":"Cerebrovascular inflammation following subarachnoid hemorrhage","volume":"88","author":"Sercombe","year":"2002","journal-title":"Jpn. J. Pharm."},{"key":"ref_22","first-page":"141","article-title":"Increase of the IL-1\u03b2 and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH","volume":"25","author":"Hendryk","year":"2004","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"562","DOI":"10.3171\/jns.1993.78.4.0562","article-title":"Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage","volume":"78","author":"Mathiesen","year":"1993","journal-title":"J. Neurosurg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1080\/01616412.1995.11740296","article-title":"Cytokine production in cerebrospinal fluid after subarachnoid haemorrhage","volume":"17","author":"Kikuchi","year":"1995","journal-title":"Neurol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3171\/jns.2006.105.3.438","article-title":"Gene expression and molecular changes in cerebral arteries following subarachnoid hemorrhage in the rat","volume":"105","author":"Vikman","year":"2006","journal-title":"J. Neurosurg."},{"key":"ref_26","first-page":"57","article-title":"Immunological response in early brain injury after SAH","volume":"110","author":"Sozen","year":"2011","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.surneu.2009.05.027","article-title":"Role of inflammation (leukocyte-endothelial cell interactions) in vasospasm after subarachnoid hemorrhage","volume":"73","author":"Chaichana","year":"2010","journal-title":"World Neurosurg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s12028-010-9432-4","article-title":"Relevance of cerebral interleukin-6 after aneurysmal subarachnoid hemorrhage","volume":"13","author":"Sarrafzadeh","year":"2010","journal-title":"Neurocrit. Care"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00401-015-1440-1","article-title":"Microglia inflict delayed brain injury after subarachnoid hemorrhage","volume":"130","author":"Schneider","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3171\/jns.1978.48.4.0515","article-title":"Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage","volume":"48","author":"Hughes","year":"1978","journal-title":"J. Neurosurg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1097\/00006123-199911000-00024","article-title":"Inflammation and intracranial aneurysms","volume":"45","author":"Chyatte","year":"1999","journal-title":"Neurosurgery"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/j.jstrokecerebrovasdis.2013.12.004","article-title":"Rosuvastatin ameliorates early brain injury after subarachnoid hemorrhage via suppression of superoxide formation and nuclear factor-\u03baB activation in rats","volume":"23","author":"Uekawa","year":"2014","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jss.2014.05.029","article-title":"Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage","volume":"192","author":"Zhang","year":"2014","journal-title":"J. Surg. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1097\/00006123-200211000-00005","article-title":"Serum von willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage","volume":"51","author":"McGirt","year":"2002","journal-title":"Neurosurgery"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1007\/s12975-011-0117-x","article-title":"Elevated peripheral neutrophils and matrix metalloproteinase 9 as biomarkers of functional outco me following subarachnoid hemorrhage","volume":"2","author":"Chou","year":"2011","journal-title":"Transl. Stroke Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1159\/000328248","article-title":"Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage","volume":"32","author":"Feiler","year":"2011","journal-title":"Cerebrovasc. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15819","DOI":"10.1523\/JNEUROSCI.3776-09.2009","article-title":"Neuroprotective role of haptoglobin after intracerebral hemorrhage","volume":"29","author":"Zhao","year":"2009","journal-title":"J. Neurosci. Off. J. Soc. Neurosc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1136\/jnnp.70.4.534","article-title":"Inflammatory cytokines in subarachnoid haemorrhage: Association with abnormal blood flow velocities in basal cerebral arteries","volume":"70","author":"Fassbender","year":"2001","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16180","DOI":"10.1523\/JNEUROSCI.3020-14.2014","article-title":"Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury","volume":"34","author":"Iliff","year":"2014","journal-title":"J. Neurosci. Off. J. Soc. Neurosc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1161\/STROKEAHA.112.678698","article-title":"Is there a cerebral lymphatic system?","volume":"44","author":"Iliff","year":"2013","journal-title":"Stroke"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1212\/01.wnl.0000200781.62172.1d","article-title":"Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage","volume":"66","author":"Borsody","year":"2006","journal-title":"Neurology"},{"key":"ref_42","first-page":"215","article-title":"Treatment of cerebral vasospasm after subarachnoid hemorrhage\u2014A review","volume":"42","author":"Wu","year":"2004","journal-title":"Acta Anaesthesiol. Taiwan"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1161\/01.STR.0000163090.59350.5a","article-title":"Patterns of cerebral infarction in aneurysmal subarachnoid hemorrhage","volume":"36","author":"Rabinstein","year":"2005","journal-title":"Stroke"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"R198","DOI":"10.1186\/cc11686","article-title":"Endothelin-receptor antagonists for aneurysmal subarachnoid hemorrhage: An updated meta-analysis of randomized controlled trials","volume":"16","author":"Ma","year":"2012","journal-title":"Crit. Care"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Konczalla, J., Kashefiolasl, S., Brawanski, N., Lescher, S., Senft, C., Platz, J., and Seifert, V. (2016). Cerebral vasospasm and delayed cerebral infarctions in 225 patients with non-aneurysmal subarachnoid hemorrhage: The underestimated risk of fisher 3 blood distribution. J. Neurointerv. Surg.","DOI":"10.1136\/neurintsurg-2015-012153"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1097\/00006123-199802000-00091","article-title":"Acute vasoconstriction after subarachnoid hemorrhage","volume":"42","author":"Bederson","year":"1998","journal-title":"Neurosurgery"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1161\/01.STR.16.4.562","article-title":"Cerebral vasospasm following aneurysmal subarachnoid hemorrhage","volume":"16","author":"Kassell","year":"1985","journal-title":"Stroke"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1055\/s-2005-923537","article-title":"Subarachnoid hemorrhage and inflammation: Bench to bedside and back","volume":"25","author":"Provencio","year":"2005","journal-title":"Semin. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jneumeth.2009.06.027","article-title":"A novel method for subarachnoid hemorrhage to induce vasospasm in mice","volume":"183","author":"Altay","year":"2009","journal-title":"J. Neurosci. Methods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0165-0270(02)00344-8","article-title":"A murine model of subarachnoid hemorrhage-induced cerebral vasospasm","volume":"123","author":"Lin","year":"2003","journal-title":"J. Neurosci. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.3171\/foc.2006.21.3.4","article-title":"Dissociation between vasospasm and functional improvement in a murine model of subarachnoid hemorrhage","volume":"21","author":"Mesis","year":"2006","journal-title":"Neurosurg. Focus"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1179\/016164102101200276","article-title":"Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: Methodological analysis","volume":"24","author":"Parra","year":"2002","journal-title":"Neurol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/978-3-319-04981-6_60","article-title":"Canine double hemorrhage model of experimental subarachnoid hemorrhage","volume":"120","author":"Mori","year":"2015","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s00701-007-1284-z","article-title":"Erythropoietin in patients with aneurysmal subarachnoid haemorrhage: A double blind randomised clinical trial","volume":"149","author":"Springborg","year":"2007","journal-title":"Acta Neurochir."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s12028-009-9308-7","article-title":"CSF neutrophils are implicated in the development of vasospasm in subarachnoid hemorrhage","volume":"12","author":"Provencio","year":"2010","journal-title":"Neurocrit. Care"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"20221","DOI":"10.1074\/jbc.M610737200","article-title":"Characterization of heme as activator of toll-like receptor 4","volume":"282","author":"Figueiredo","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.drudis.2007.11.010","article-title":"New insights into the causes and therapy of cerebral vasospasm following subarachnoid hemorrhage","volume":"13","author":"Crowley","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/1742-2094-10-83","article-title":"The role of microglia and the tlr4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage","volume":"10","author":"Hanafy","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1172\/JCI11837","article-title":"Toll-like receptor-mediated NF-\u03baB activation: A phylogenetically conserved paradigm in innate immunity","volume":"107","author":"Zhang","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nri2079","article-title":"The family of five: Tir-domain-containing adaptors in toll-like receptor signalling","volume":"7","author":"Bowie","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/1742-2094-10-157","article-title":"Tamoxifen as an effective neuroprotectant against early brain injury and learning deficits induced by subarachnoid hemorrhage: Possible involvement of inflammatory signaling","volume":"10","author":"Sun","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_62","first-page":"e519","article-title":"Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage","volume":"41","author":"Macdonald","year":"2010","journal-title":"Stroke"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kooijman, E., Nijboer, C.H., van Velthoven, C.T., Mol, W., Dijkhuizen, R.M., Kesecioglu, J., and Heijnen, C.J. (2014). Long-term functional consequences and ongoing cerebral inflammation after subarachnoid hemorrhage in the rat. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090584"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nrn2480","article-title":"Remyelination in the CNS: From biology to therapy","volume":"9","author":"Franklin","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/ana.21359","article-title":"Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury","volume":"63","author":"Segovia","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00415-008-1004-6","article-title":"The biology of cns remyelination: The key to therapeutic advances","volume":"255","author":"Franklin","year":"2008","journal-title":"J. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s10522-013-9465-0","article-title":"Preclinical models of stroke in aged animals with or without comorbidities: Role of neuroinflammation","volume":"14","author":"Buga","year":"2013","journal-title":"Biogerontology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1038\/jcbfm.2015.75","article-title":"20-hete is associated with unfavorable outcomes in subarachnoid hemorrhage patients","volume":"35","author":"Donnelly","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/jcbfm.2014.195","article-title":"Genetic markers in the EET metabolic pathway are associated with outcomes in patients with aneurysmal subarachnoid hemorrhage","volume":"35","author":"Donnelly","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.mgene.2014.07.001","article-title":"Association of versican (VCAN) gene polymorphisms rs251124 and rs2287926 (g428d), with intracranial aneurysm","volume":"2","author":"Sathyan","year":"2014","journal-title":"Meta Gene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.wneu.2015.01.002","article-title":"The genetics of aneurysms: A complex pathophysiology requiring complex analysis","volume":"83","author":"McDowell","year":"2015","journal-title":"World Neurosurg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/01.ccx.0000155354.78617.91","article-title":"Genetic influences on outcome following acute neurological insults","volume":"11","author":"Waters","year":"2005","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1073\/pnas.1412833112","article-title":"Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage","volume":"112","author":"Leclerc","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.3171\/JNS.2008.109.12.1019","article-title":"Psychosocial and neurocognitive performance after spontaneous nonaneurysmal subarachnoid hemorrhage related to the apoe-epsilon4 genotype: A prospective 5-year follow-up study","volume":"109","author":"Alfieri","year":"2008","journal-title":"J. Neurosurg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.pjnns.2014.07.007","article-title":"The AGTR1 gene A1166C polymorphism as a risk factor and outcome predictor of primary intracerebral and aneurysmal subarachnoid hemorrhages","volume":"48","author":"Adamski","year":"2014","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/1742-2094-11-106","article-title":"Early release of high-mobility group box 1 (hmgb1) from neurons in experimental subarachnoid hemorrhage in vivo and in vitro","volume":"11","author":"Sun","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1742-2094-11-77","article-title":"Critical role of TNF-\u03b1 in cerebral aneurysm formation and progression to rupture","volume":"11","author":"Starke","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.nbd.2013.06.011","article-title":"P2x7r\/cryopyrin inflammasome axis inhibition reduces neuroinflammation after SAH","volume":"58","author":"Chen","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.1161\/STROKEAHA.113.002904","article-title":"Inhibition of the SUR1-TRPM4 channel reduces neuroinflammation and cognitive impairment in subarachnoid hemorrhage","volume":"44","author":"Tosun","year":"2013","journal-title":"Stroke"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1161\/STROKEAHA.113.002465","article-title":"Migraine and hemorrhagic stroke: A meta-analysis","volume":"44","author":"Sacco","year":"2013","journal-title":"Stroke"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12028-009-9232-x","article-title":"Diabetes mellitus increases risk of vasospasm following aneurysmal subarachnoid hemorrhage independent of glycemic control","volume":"11","author":"Dumont","year":"2009","journal-title":"Neurocrit. Care"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1227\/01.NEU.0000249271.56816.03","article-title":"Subarachnoid clot volume correlates with age, neurological grade, and blood pressure","volume":"60","author":"Rosen","year":"2007","journal-title":"Neurosurgery"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.3949\/ccjm.75.Suppl_2.S26","article-title":"Inflammation as a link between brain injury and heart damage: The model of subarachnoid hemorrhage","volume":"75","author":"Mashaly","year":"2008","journal-title":"Cleve. Clin. J. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1471-2202-15-33","article-title":"Ischemia modified albumin increase indicating cardiac damage after experimental subarachnoid hemorrhage","volume":"15","author":"Acikgoz","year":"2014","journal-title":"BMC Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/1742-2094-8-103","article-title":"Reduction of neutrophil activity decreases early microvascular injury after subarachnoid haemorrhage","volume":"8","author":"Friedrich","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1742-2094-9-28","article-title":"Functional analysis of pro-inflammatory properties within the cerebrospinal fluid after subarachnoid hemorrhage in vivo and in vitro","volume":"9","author":"Schneider","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.neuroscience.2015.04.045","article-title":"Models and mechanisms for hippocampal dysfunction in obesity and diabetes","volume":"309","author":"Stranahan","year":"2015","journal-title":"Neuroscience"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neuropharm.2014.12.023","article-title":"Obesity, adipokines and neuroinflammation","volume":"96","author":"Inoue","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.bbi.2011.02.008","article-title":"Brain inflammation is induced by co-morbidities and risk factors for stroke","volume":"25","author":"Drake","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"225","DOI":"10.14740\/jocmr2073w","article-title":"Everyday memory in microsurgically treated patients after subarachnoid hemorrhage","volume":"7","author":"Koso","year":"2015","journal-title":"J. Clin. Med. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1161\/STROKEAHA.113.003072","article-title":"Roles of hypertension in the rupture of intracranial aneurysms","volume":"45","author":"Tada","year":"2014","journal-title":"Stroke"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Bashir, A., Andresen, M., Bartek, J., Cortsen, M., Eskesen, V., and Wagner, A. (2016). Intra-arterial nimodipine for cerebral vasospasm after subarachnoid haemorrhage: Influence on clinical course and predictors of clinical outcome. Neuroradiol. J.","DOI":"10.1177\/1971400915626429"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-2094-11-1","article-title":"The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: A phase ii randomised controlled trial","volume":"11","author":"Singh","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.neuroscience.2012.11.024","article-title":"Expression of NR2B in different brain regions and effect of NR2B antagonism on learning deficits after experimental subarachnoid hemorrhage","volume":"231","author":"Chen","year":"2013","journal-title":"Neuroscience"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.brainres.2012.10.061","article-title":"The neuro-behavioral profile in rats after subarachnoid hemorrhage","volume":"1491","author":"Boyko","year":"2013","journal-title":"Brain Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1471-2202-14-34","article-title":"Early events triggering delayed vasoconstrictor receptor upregulation and cerebral ischemia after subarachnoid hemorrhage","volume":"14","author":"Povlsen","year":"2013","journal-title":"BMC Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/jcbfm.2014.205","article-title":"Mek1\/2 inhibitor u0126 but not endothelin receptor antagonist clazosentan reduces upregulation of cerebrovascular contractile receptors and delayed cerebral ischemia, and improves outcome after subarachnoid hemorrhage in rats","volume":"35","author":"Povlsen","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1186\/1742-2094-9-274","article-title":"Regulation of enhanced cerebrovascular expression of proinflammatory mediators in experimental subarachnoid hemorrhage via the mitogen-activated protein kinase kinase\/extracellular signal-regulated kinase pathway","volume":"9","author":"Maddahi","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1111\/j.1471-4159.2009.06077.x","article-title":"Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in rats","volume":"109","author":"Tian","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/978-3-7091-0693-8_45","article-title":"Tamoxifen treatment for intracerebral hemorrhage","volume":"111","author":"Xie","year":"2011","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1046\/j.1471-4159.2001.00198.x","article-title":"Tamoxifen inhibits nitrotyrosine formation after reversible middle cerebral artery occlusion in the rat","volume":"76","author":"Osuka","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ejphar.2003.10.048","article-title":"Treatment with tamoxifen reduces hypoxic-ischemic brain injury in neonatal rats","volume":"484","author":"Feng","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.brainres.2015.01.047","article-title":"Vap-1 blockade prevents subarachnoid hemorrhage-associated cerebrovascular dilating dysfunction via repression of a neutrophil recruitment-related mechanism","volume":"1603","author":"Xu","year":"2015","journal-title":"Brain Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12974-015-0234-7","article-title":"Protective role of fingolimod (FTY720) in rats subjected to subarachnoid hemorrhage","volume":"12","author":"Xu","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.surneu.2005.04.038","article-title":"Monoclonal antibody against e selectin attenuates subarachnoid hemorrhage-induced cerebral vasospasm","volume":"64","author":"Lin","year":"2005","journal-title":"Surg. Neuro."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3171\/jns.2004.101.1.0088","article-title":"Prevention of vasospasm by anti-CD11\/CD18 monoclonal antibody therapy following subarachnoid hemorrhage in rabbits","volume":"101","author":"Pradilla","year":"2004","journal-title":"J. Neurosurg."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jneuroim.2010.10.016","article-title":"Depletion of Ly6g\/C (+) cells ameliorates delayed cerebral vasospasm in subarachnoid hemorrhage","volume":"232","author":"Provencio","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1189\/jlb.0407247","article-title":"Use of ly6g-specific monoclonal antibody to deplete neutrophils in mice","volume":"83","author":"Daley","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s12975-012-0166-9","article-title":"Heparin reduces neuroinflammation and transsynaptic neuronal apoptosis in a model of subarachnoid hemorrhage","volume":"3","author":"Simard","year":"2012","journal-title":"Transl. Stroke Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.3390\/ph6101287","article-title":"Glibenclamide for the treatment of acute CNS injury","volume":"6","author":"Kurland","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1227\/01.NEU.0000068863.37133.9E","article-title":"Cerebral vasospasm after subarachnoid hemorrhage: Putative role of inflammation","volume":"53","author":"Dumont","year":"2003","journal-title":"Neurosurgery"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3171\/jns.1998.89.4.0559","article-title":"Detection of soluble e-selectin, icam-1, vcam-1, and l-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage","volume":"89","author":"Polin","year":"1998","journal-title":"J. Neurosurg."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jns.2011.03.006","article-title":"Therapeutic potential of peroxisome proliferator-activated receptor gamma agonist rosiglitazone in cerebral vasospasm after a rat experimental subarachnoid hemorrhage model","volume":"305","author":"Wu","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.brainres.2010.01.073","article-title":"Peroxisome proliferator-activated receptor gamma agonist rosiglitazone attenuates oxyhemoglobin-induced toll-like receptor 4 expression in vascular smooth muscle cells","volume":"1322","author":"Wu","year":"2010","journal-title":"Brain Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1089\/neu.2006.0181","article-title":"NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat","volume":"24","author":"Germano","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1227\/NEU.0000000000000080","article-title":"A glutamate receptor antagonist, S-4-Carboxyphenylglycine (S-4-CPG), inhibits vasospasm after subarachnoid hemorrhage in haptoglobin 2-2 mice","volume":"73","author":"Pradilla","year":"2013","journal-title":"Neurosurgery"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/4\/497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:21:44Z","timestamp":1760210504000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/4\/497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,2]]},"references-count":116,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,4]]}},"alternative-id":["ijms17040497"],"URL":"https:\/\/doi.org\/10.3390\/ijms17040497","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,2]]}}}