{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T14:18:58Z","timestamp":1770387538023,"version":"3.49.0"},"reference-count":106,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"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>Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.<\/jats:p>","DOI":"10.3390\/ijms22116141","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T13:25:43Z","timestamp":1623072343000},"page":"6141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations\u2014A Short Overview"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4776-7247","authenticated-orcid":false,"given":"Teodora Larisa","family":"Timis","sequence":"first","affiliation":[{"name":"Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7730-338X","authenticated-orcid":false,"given":"Ioan Alexandru","family":"Florian","sequence":"additional","affiliation":[{"name":"Clinic of Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj County Emergency Clinical Hospital, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergiu","family":"Susman","sequence":"additional","affiliation":[{"name":"Department of Histology, Iuliu Hatieganu, University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7127-0946","authenticated-orcid":false,"given":"Ioan Stefan","family":"Florian","sequence":"additional","affiliation":[{"name":"Clinic of Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj County Emergency Clinical Hospital, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jocn.2020.09.048","article-title":"Epidemiologic and anatomic aspects comparing incidental and ruptured intracranial aneurysms: A single centre experience","volume":"81","author":"Haase","year":"2020","journal-title":"J. Clin. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1161\/STROKEAHA.113.001838","article-title":"Natural History of unruptured Intracranial aneurysms: A long-term follow-up study","volume":"44","author":"Juvela","year":"2013","journal-title":"Stroke"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1212\/CON.0000000000000418","article-title":"Management of Unruptured Intracranial Aneurysms and Cerebrovascular Malformations","volume":"23","author":"Flemming","year":"2017","journal-title":"Contin. Lifelong Learn. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/neuros\/nyaa454","article-title":"Survival, Dependency, and Health-Related Quality of Life in Patients with Ruptured Intracranial Aneurysm: 10-Year Follow-up of the United Kingdom Cohort of the International Subarachnoid Aneurysm Trial","volume":"88","author":"Hua","year":"2020","journal-title":"Neurosurgery"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"63","DOI":"10.5469\/neuroint.2014.9.2.63","article-title":"Clinical Practice Guideline for the Management of Intracranial Aneurysms","volume":"9","author":"Jeong","year":"2014","journal-title":"Neurointervention"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15492","DOI":"10.1038\/s41598-020-72309-8","article-title":"Physiologic blood flow is turbulent","volume":"10","author":"Saqr","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s40478-016-0318-3","article-title":"Sustained expression of MCP-1 by low wall shear stress loading concomitant with turbulent flow on endothelial cells of intracranial aneurysm","volume":"4","author":"Aoki","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e829","DOI":"10.1016\/j.wneu.2020.06.047","article-title":"Connective Tissue Abnormalities in Patients with Ruptured Intracranial Aneurysms and No Known Systemic Connective Tissue Disorder","volume":"141","author":"Yerramilli","year":"2020","journal-title":"World Neurosurg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12974-021-02085-3","article-title":"Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)","volume":"18","author":"Heinz","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.4103\/1673-5374.303028","article-title":"Microglia accumulation and activation after subarachnoid hemorrhage","volume":"16","author":"Wong","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1212\/CON.0000000000000835","article-title":"Management of Unruptured Cerebral Aneurysms and Arteriovenous Malformations","volume":"26","author":"Ruigrok","year":"2020","journal-title":"Contin. Lifelong Learn. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.3171\/2014.6.FOCUS14250","article-title":"Natural history of brain arteriovenous malformations: A systematic review","volume":"37","author":"Abecassis","year":"2014","journal-title":"Neurosurg. Focus"},{"key":"ref_13","first-page":"313","article-title":"Vascular Malformations (Arteriovenous Malformations and Dural Arteriovenous Fistulas)","volume":"Volume 20","author":"Ellenbogen","year":"2018","journal-title":"Principles of Neurological Surgery"},{"key":"ref_14","unstructured":"Ellenbogen, R.G., Sekhar, L.N., and Kitchen, N.D. (2018). Cavernous Malformations of the Brain and Spinal Cord. Principles of Neurological Surgery, Elsevier Inc."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Florian, I.S. (2020). Cavernous Malformations of the Pineal Region: Overview, Management, and Controversies. Pineal Region Lesions, Springer.","DOI":"10.1007\/978-3-030-50913-2"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.4103\/1673-5374.313034","article-title":"Microglia activation: A role for mitochondrial DNA?","volume":"16","author":"Nasi","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12974-021-02142-x","article-title":"Minocycline attenuation of rat corpus callosum abnormality mediated by low-dose lipopolysaccharide-induced microglia activation","volume":"18","author":"Zhang","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"631827","DOI":"10.3389\/fnagi.2021.631827","article-title":"Interplay Between Microglia and Alzheimer\u2019s Disease\u2014Focus on the Most Relevant Risks: APOE Genotype, Sex and Age","volume":"13","author":"Chen","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nature09615","article-title":"The myeloid cells of the central nervous system parenchyma","volume":"468","author":"Ransohoff","year":"2010","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1152\/physrev.00011.2010","article-title":"Physiology of Microglia","volume":"91","author":"Kettenmann","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_21","first-page":"10","article-title":"Microglia-insights into immune system structure, function, and reactivity in the central nervous system","volume":"26","author":"Wirenfeldt","year":"2011","journal-title":"Histol. Histopathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1126\/science.1110647","article-title":"Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo","volume":"308","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"566","DOI":"10.3389\/fnhum.2016.00566","article-title":"The Indispensable Roles of Microglia and Astrocytes during Brain Development","volume":"10","author":"Reemst","year":"2016","journal-title":"Front. Hum. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/2045-824X-5-12","article-title":"Correction: The importance of microglia in the development of the vasculature in the central nervous system","volume":"5","author":"Arnold","year":"2013","journal-title":"Vasc. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.ceb.2010.08.010","article-title":"Dynamics of endothelial cell behavior in sprouting angiogenesis","volume":"22","author":"Eilken","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rymo, S.F., Gerhardt, H., Sand, F.W., Lang, R., Uv, A., and Betsholtz, C. (2011). A Two-way communication between microglial cells and angiogenic sprouts regulates angiogenesis in aortic ring cultures. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015846"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1111\/j.1471-4159.2011.07504.x","article-title":"Physiological roles of microglia during development","volume":"119","author":"Pascual","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/s41467-020-14787-y","article-title":"Microglia control vascular architecture via a TGF\u03b21 dependent paracrine mechanism linked to tissue mechanics","volume":"11","author":"Dudiki","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1136\/neurintsurg-2016-012911","article-title":"M1 macrophages are required for murine cerebral aneurysm formation","volume":"10","author":"Nowicki","year":"2018","journal-title":"J. NeuroInterventional Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/1742-2094-9-222","article-title":"Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: Preliminary results","volume":"9","author":"Hasan","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jocn.2019.05.027","article-title":"Histological analysis of infiltrating macrophages in the cerebral aneurysm walls","volume":"67","author":"Yamashiro","year":"2019","journal-title":"J. Clin. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"825","DOI":"10.3171\/2013.6.JNS09329a","article-title":"Erratum: Toll-like receptor 4 expression during cerebral aneurysm formation","volume":"119","author":"Nishimura","year":"2013","journal-title":"J. Neurosurg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1161\/HYPERTENSIONAHA.118.12595","article-title":"TLR4 (Toll-Like Receptor 4) Mediates the Development of Intracranial Aneurysm Rupture","volume":"75","author":"Mitsui","year":"2020","journal-title":"Hypertension"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1227\/NEU.0b013e318210f001","article-title":"Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: An emerging regulative role of toll-like receptor signaling and nuclear factor-\u03baB, hypoxia-Inducible factor-1A, and ETS transcription factors","volume":"68","author":"Kurki","year":"2011","journal-title":"Neurosurgery"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"eaah6037","DOI":"10.1126\/scisignal.aah6037","article-title":"Prostaglandin E2\u2013EP2\u2013NF-\u03baB signaling in macrophages as a potential therapeutic target for intracranial aneurysms","volume":"10","author":"Aoki","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1111\/j.1476-5381.2011.01358.x","article-title":"PGE2-EP2signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF-\u03baB","volume":"163","author":"Aoki","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1161\/STROKEAHA.114.007722","article-title":"Protective Role of Peroxisome Proliferator\u2013Activated Receptor-\u03b3 in the Development of Intracranial Aneurysm Rupture","volume":"46","author":"Shimada","year":"2015","journal-title":"Stroke"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1161\/HYPERTENSIONAHA.115.05332","article-title":"Smooth Muscle Peroxisome Proliferator\u2013Activated Receptor \u03b3 Plays a Critical Role in Formation and Rupture of Cerebral Aneurysms in Mice In Vivo","volume":"66","author":"Hasan","year":"2015","journal-title":"Hypertension"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e004777","DOI":"10.1161\/JAHA.116.004777","article-title":"Dipeptidyl Peptidase-4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation","volume":"6","author":"Ikedo","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_40","first-page":"E214","article-title":"DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-\u03baB activation","volume":"309","author":"Shinjo","year":"2015","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"F878","DOI":"10.1152\/ajprenal.00590.2014","article-title":"Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury","volume":"308","author":"Higashijima","year":"2015","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"698","DOI":"10.5551\/jat.42481","article-title":"Suppression of Abdominal Aortic Aneurysm Formation in Mice by Teneligliptin, a Dipeptidyl Peptidase-4 Inhibitor","volume":"25","author":"Takahara","year":"2018","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_43","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_44","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s13311-019-00829-x","article-title":"Aneurysmal Subarachnoid Hemorrhage: An Overview of Inflammation-Induced Cellular Changes","volume":"17","author":"Coulibaly","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.yexcr.2017.11.002","article-title":"Erythropoietin ameliorates early brain injury after subarachnoid haemorrhage by modulating microglia polarization via the EPOR\/JAK2-STAT3 pathway","volume":"361","author":"Wei","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s10571-019-00760-x","article-title":"Inhibition of mTOR Alleviates Early Brain Injury After Subarachnoid Hemorrhage Via Relieving Excessive Mitochondrial Fission","volume":"40","author":"Li","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jns.2016.06.021","article-title":"Inhibition of mammalian target of rapamycin attenuates early brain injury through modulating microglial polarization after experimental subarachnoid hemorrhage in rats","volume":"367","author":"You","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1281","DOI":"10.1212\/WNL.0000000000008868","article-title":"Soluble vascular endothelial-cadherin in CSF after subarachnoid hemorrhage","volume":"94","author":"Takase","year":"2020","journal-title":"Neurology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.brainres.2016.10.006","article-title":"Expression and cell distribution of leukotriene B4 receptor 1 in the rat brain cortex after experimental subarachnoid hemorrhage","volume":"1652","author":"Ye","year":"2016","journal-title":"Brain Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.2353\/ajpath.2010.090839","article-title":"The LTB4-BLT1 Axis Mediates Neutrophil Infiltration and Secondary Injury in Experimental Spinal Cord Injury","volume":"176","author":"Saiwai","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s12975-010-0052-2","article-title":"Subarachnoid Hemorrhage Induces Gliosis and Increased Expression of the Pro-inflammatory Cytokine High Mobility Group Box 1 Protein","volume":"2","author":"Murakami","year":"2010","journal-title":"Transl. Stroke Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/s12028-009-9276-y","article-title":"High-Mobility Group Box 1 Protein in CSF of Patients with Subarachnoid Hemorrhage","volume":"11","author":"Nakahara","year":"2009","journal-title":"Neurocrit. Care"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"E10","DOI":"10.3171\/2009.10.FOCUS09223","article-title":"Elucidating novel mechanisms of brain injury following subarachnoid hemorrhage: An emerging role for neuroproteomics","volume":"28","author":"King","year":"2010","journal-title":"Neurosurg. Focus"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1016\/j.jstrokecerebrovasdis.2015.05.002","article-title":"HMGB1 Level in Cerebrospinal Fluid as a Marker of Treatment Outcome in Patients with Acute Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage","volume":"24","author":"Jankowski","year":"2015","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3934\/Neuroscience.2019.4.316","article-title":"Elucidating the novel biomarker and therapeutic potentials of High-mobility group box 1 in Subarachnoid hemorrhage: A review","volume":"6","author":"Richard","year":"2019","journal-title":"AIMS Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jocn.2015.06.034","article-title":"Expression of high-mobility group box-1 (HMGB1) in the basilar artery after experimental subarachnoid hemorrhage","volume":"27","author":"Zhao","year":"2016","journal-title":"J. Clin. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"134338","DOI":"10.1016\/j.neulet.2019.134338","article-title":"Anti-high mobility group box-1 antibody attenuated vascular smooth muscle cell phenotypic switching and vascular remodelling after subarachnoid haemorrhage in rats","volume":"708","author":"Wang","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11809","DOI":"10.1038\/s41598-020-68861-y","article-title":"Preliminary results in the analysis of the immune response after aneurysmal subarachnoid hemorrhage","volume":"10","author":"Roa","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1179\/174313209X382395","article-title":"Peri-operative measures for treatment and prevention of cerebral vasospasm following subarachnoid hemorrhage","volume":"31","author":"Alaraj","year":"2009","journal-title":"Neurol. Res."},{"key":"ref_61","first-page":"1","article-title":"An overview of pharmacotherapy for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage","volume":"13","author":"Maruhashi","year":"2021","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"868","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_63","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12974-018-1118-4","article-title":"Peroxiredoxin 2 activates microglia by interacting with Toll-like receptor 4 after subarachnoid hemorrhage","volume":"15","author":"Lu","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.brainres.2013.05.010","article-title":"Expression and cell distribution of myeloid differentiation primary response protein 88 in the cerebral cortex following experimental subarachnoid hemorrhage in rats: A pilot study","volume":"1520","author":"Sun","year":"2013","journal-title":"Brain Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.brainresbull.2020.04.003","article-title":"Cerebral cavernous malformation 3 relieves subarachnoid hemorrhage-induced neuroinflammation in rats through inhibiting NF-kB signaling pathway","volume":"160","author":"Peng","year":"2020","journal-title":"Brain Res. Bull."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.3389\/fnins.2019.01223","article-title":"Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage","volume":"13","author":"Gao","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3389\/fncel.2020.00210","article-title":"Hydrogen Sulfide Reduces Cognitive Impairment in Rats After Subarachnoid Hemorrhage by Ameliorating Neuroinflammation Mediated by the TLR4\/NF-\u03baB Pathway in Microglia","volume":"14","author":"Duan","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.intimp.2015.05.024","article-title":"Apigenin protects blood\u2013brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats","volume":"28","author":"Zhang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"46577","DOI":"10.1038\/srep46577","article-title":"High-Throughput Sequencing and Co-Expression Network Analysis of lncRNAs and mRNAs in Early Brain Injury Following Experimental Subarachnoid Haemorrhage","volume":"7","author":"Peng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s00701-010-0865-5","article-title":"6-Mercaptopurine reverses experimental vasospasm and alleviates the production of endothelins in NO-independent mechanism\u2014A laboratory study","volume":"153","author":"Chang","year":"2010","journal-title":"Acta Neurochir."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00701-010-0602-0","article-title":"6-Mercaptopurine attenuates adhesive molecules in experimental vasospasm","volume":"152","author":"Chang","year":"2010","journal-title":"Acta Neurochir."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1172\/JCI78443","article-title":"Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1","volume":"125","author":"Schallner","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kaiser, S., Selzner, L., Weber, J., and Schallner, N. (2020). Carbon monoxide controls microglial erythrophagocytosis by regulating CD36 surface expression to reduce the severity of hemorrhagic injury. Glia.","DOI":"10.1002\/glia.23864"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s12974-016-0709-1","article-title":"Heme oxygenase-1-mediated neuroprotection in subarachnoid hemorrhage via intracerebroventricular deferoxamine","volume":"13","author":"Leblanc","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","unstructured":"Kooijman, E., Nijboer, C.H., Van Velthoven, C.T.J., Mol, W., Dijkhuizen, R.M., Kesecio\u011flu, 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_77","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s11011-014-9531-6","article-title":"The role of the microglia in acute CNS injury","volume":"30","author":"Kawabori","year":"2015","journal-title":"Metab. Brain Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6","DOI":"10.4103\/1673-5374.286954","article-title":"Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke","volume":"16","author":"Wang","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/s12975-016-0485-3","article-title":"Intravascular Inflammation Triggers Intracerebral Activated Microglia and Contributes to Secondary Brain Injury After Experimental Subarachnoid Hemorrhage (eSAH)","volume":"8","author":"Atangana","year":"2016","journal-title":"Transl. Stroke Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/dneu.22576","article-title":"Microglial interactions with the neurovascular system in physiology and pathology","volume":"78","author":"Zhao","year":"2018","journal-title":"Dev. Neurobiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40478-019-0665-y","article-title":"Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes\/macrophages in health and glioma","volume":"7","author":"Haage","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Schroeter, C., Herrmann, A., Bock, S., Vogelsang, A., Eichler, S., Albrecht, P., Meuth, S., and Ruck, T. (2021). One Brain\u2014All Cells: A Comprehensive Protocol to Isolate All Principal CNS-Resident Cell Types from Brain and Spinal Cord of Adult Healthy and EAE Mice. Cells, 10.","DOI":"10.3390\/cells10030651"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ma, L., Zhu, W., Zhan, L., Zhang, R., Li, Q., Bao, C., Weiss, M., Wang, A., and Su, H. (2018). Abstract 76: Transient Depletion of Microglia Reduces the Severity of Brain Arteriovenous Malformation in a Mouse Model. Stroke, 49.","DOI":"10.1161\/str.49.suppl_1.76"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"A191","DOI":"10.1161\/str.46.suppl_1.191","article-title":"Abstract 191: Persistent Infiltration of Active Microglia in Brain Arterio-venous Malformation Causes Unresolved Inflammation and Lesion Progression","volume":"46","author":"Zhang","year":"2015","journal-title":"Stroke"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1227\/01.neu.0000333306.64683.b5","article-title":"Evidence of inflam-matory cell involvement in brain arteriovenous malformations","volume":"62","author":"Chen","year":"2008","journal-title":"Neurosurgery"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s10456-016-9519-4","article-title":"Persistent infiltration and pro-inflammatory differentiation of monocytes cause unresolved inflammation in brain arteriovenous malformation","volume":"19","author":"Zhang","year":"2016","journal-title":"Angiogenesis"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1161\/ATVBAHA.112.300485","article-title":"Reduced mural cell coverage and impaired vessel integrity after angiogenic stimulation in the Alk1-deficient brain","volume":"33","author":"Chen","year":"2013","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1161\/STROKEAHA.113.003655","article-title":"De Novo Cerebrovascular Malformation in the Adult Mouse After Endothelial Alk1 Deletion and Angiogenic Stimulation","volume":"45","author":"Chen","year":"2014","journal-title":"Stroke"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3171\/JNS-07\/09\/0495","article-title":"Electrocorticography discharge patterns in patients with a cavernous hemangioma and pharmacoresistent epilepsy","volume":"107","author":"Ferrier","year":"2007","journal-title":"J. Neurosurg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/2051-5960-2-71","article-title":"Evidence for mTOR pathway activation in a spectrum of epilepsy-associated pathologies","volume":"2","author":"Liu","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jneuroim.2006.01.002","article-title":"Evidence of activated microglia in focal cortical dysplasia","volume":"173","author":"Boer","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/jon.12477","article-title":"Assessing Inflammation in Acute Intracerebral Hemorrhage with PK11195 PET and Dynamic Contrast-Enhanced MRI","volume":"28","author":"Abid","year":"2017","journal-title":"J. Neuroimaging"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.nbd.2017.03.016","article-title":"Alternative activation-skewed microglia\/macrophages promote hematoma resolution in experimental intracerebral hemorrhage","volume":"103","author":"Chang","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/jnc.12974","article-title":"Cleaning up after ICH: The role of Nrf2 in modulating microglia function and hematoma clearance","volume":"133","author":"Zhao","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/ana.21097","article-title":"Hematoma resolution as a target for intracerebral hemorrhage treatment: Role for peroxisome proliferator-activated receptor \u03b3 in microglia\/macrophages","volume":"61","author":"Zhao","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_96","first-page":"S92","article-title":"Hematoma Resolution as a Therapeutic Target: The Role of Microglia\/Macrophages","volume":"40","author":"Zhao","year":"2008","journal-title":"Stroke"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/cns.13620","article-title":"Microglial\/Macrophage polarization and function in brain injury and repair after stroke","volume":"27","author":"Lyu","year":"2021","journal-title":"CNS Neurosci. Ther."},{"key":"ref_98","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_99","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3171\/2009.3.JNS081332","article-title":"Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: A Phase II randomized, double-blind, placebo-controlled trial","volume":"111","author":"Tseng","year":"2009","journal-title":"J. Neurosurg."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Helbok, R., Shaker, E., Beer, R., Chemelli, A., Sojer, M., Sohm, F., Broessner, G., Lackner, P., Beck, M., and Zangerle, A. (2012). High dose Erythropoietin increases Brain Tissue Oxygen Tension in Severe Vasospasm after Subarachnoid Hemorrhage. BMC Neurol., 12.","DOI":"10.1186\/1471-2377-12-32"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.neuron.2017.03.042","article-title":"iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases","volume":"94","author":"Abud","year":"2017","journal-title":"Neuron"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1016\/j.stemcr.2017.05.017","article-title":"A Highly Efficient Human Pluripotent Stem Cell Microglia Model Displays a Neuronal-Co-culture-Specific Expression Profile and Inflammatory Response","volume":"8","author":"Haenseler","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1038\/nm.4189","article-title":"Efficient derivation of microglia-like cells from human pluripotent stem cells","volume":"22","author":"Muffat","year":"2016","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41418-020-0566-4","article-title":"Brain Organoids: An Ensemble of Bioassays to Investigate Human Neurodevelopment and Disease","volume":"28","author":"Sidhaye","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/s41592-019-0586-5","article-title":"Engineering of Human Brain Organoids with a Functional Vascular-Like System","volume":"16","author":"Cakir","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nbt.4133","article-title":"Brain organoids get vascularized","volume":"36","author":"Lancaster","year":"2018","journal-title":"Nat. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6141\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:11:38Z","timestamp":1760163098000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":106,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22116141"],"URL":"https:\/\/doi.org\/10.3390\/ijms22116141","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,7]]}}}