{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:57:24Z","timestamp":1786377444005,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T00:00:00Z","timestamp":1618704000000},"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>Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4) signaling pathway. TLRs are pattern recognition receptors that are usually activated by the damage-associated molecular pattern molecules (DAMPs). Sterile inflammation is triggered by the endogenous DAMPs released in response to global cerebral ischemia and from extravasated blood after subarachnoid hemorrhage (SAH). In this review, we highlight the importance of the neuroinflammatory role of the MyD88 in the SAH. We also explore a few possible pharmacological agents that can be used to decrease SAH-associated neuroinflammation by modulating the MyD88 dependent functions. Pharmacological agents such as flavonoids, melatonin, fluoxetine, pentoxifylline and progesterone have been investigated experimentally to reduce the SAH-associated inflammation. Inhibition of the MyD88 not only reduces the expression of pro-inflammatory cytokines, but also potentially inhibits other processes that can augment the SAH associated inflammation. Further investigations are required to translate these findings in the clinical setting.<\/jats:p>","DOI":"10.3390\/ijms22084185","type":"journal-article","created":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T22:15:13Z","timestamp":1618784113000},"page":"4185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review"],"prefix":"10.3390","volume":"22","author":[{"given":"Hammad","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, Imran Idrees College of Pharmacy, University of the Punjab, Sialkot 51310, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-2730","authenticated-orcid":false,"given":"Mahtab Ahmad","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Central Punjab (UCP), Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6021-1841","authenticated-orcid":false,"given":"Ulf Dietrich","family":"Kahlert","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Heinrich-Heine University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Niemel\u00e4","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Helsinki and University Hospital, FI-00029 HUS Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"H\u00e4nggi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Heinrich-Heine University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafqat Rasul","family":"Chaudhry","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Heinrich-Heine University of D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Department of Neurosurgery, University of Helsinki and University Hospital, FI-00029 HUS Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nrneurol.2013.246","article-title":"Delayed neurological deterioration after subarachnoid haemorrhage","volume":"10","author":"Macdonald","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4103\/2152-7806.198738","article-title":"Management of aneurysmal subarachnoid hemorrhage: State of the art and future perspectives","volume":"8","author":"Grasso","year":"2017","journal-title":"Surg. Neurol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nrneurol.2015.228","article-title":"Controversies in epidemiology of intracranial aneurysms and SAH","volume":"12","author":"Korja","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"836","DOI":"10.2174\/1570159X13666150518235504","article-title":"Tyrosine Kinase Inhibitor as a new Therapy for Ischemic Stroke and other Neurologic Diseases: Is there any Hope for a Better Outcome?","volume":"13","author":"Rusiecka","year":"2015","journal-title":"Curr. Neuropharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nrneurol.2016.150","article-title":"Unruptured intracranial aneurysms: Development, rupture and preventive management","volume":"12","author":"Etminan","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1007\/s00134-014-3483-5","article-title":"Understanding the disease: Aneurysmal subarachnoid hemorrhage","volume":"40","author":"Macdonald","year":"2014","journal-title":"Intensiv. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.mito.2018.12.001","article-title":"Temporal profile of serum mitochondrial DNA (mtDNA) in patients with aneurysmal subarachnoid hemorrhage (aSAH)","volume":"47","author":"Chaudhry","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1023","DOI":"10.1097\/CCM.0000000000003319","article-title":"Systemic High-Mobility Group Box-1: A Novel Predictive Biomarker for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage*","volume":"46","author":"Chaudhry","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chaudhry, S.R., Hafez, A., Jahromi, B.R., Kinfe, T.M., Lamprecht, A., Niemel\u00e4, M., and Muhammad, S. (2018). Role of Damage Associated Molecular Pattern Molecules (DAMPs) in Aneurysmal Subarachnoid Hemorrhage (aSAH). Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072035"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.wneu.2018.12.061","article-title":"Sterile Inflammation, Potential Target in Aneurysmal Subarachnoid Hemorrhage","volume":"123","author":"Chaudhry","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Muhammad, S., Chaudhry, S.R., Kahlert, U.D., Lehecka, M., Korja, M., Niemel\u00e4, M., and H\u00e4nggi, D. (2020). Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082709"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/sj.jcbfm.9600283","article-title":"Mechanisms of early brain injury after subarachnoid hemorrhage","volume":"26","author":"Cahill","year":"2006","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_13","first-page":"S86","article-title":"Subarachnoid Hemorrhage: Is It Time for a New Direction?","volume":"40","author":"Cahill","year":"2008","journal-title":"Stroke"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.wneu.2014.06.031","article-title":"Medical Complications After Aneurysmal Subarachnoid Hemorrhage: An Emerging Contributor to Poor Outcome","volume":"83","author":"Etminan","year":"2015","journal-title":"World Neurosurg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41577-019-0215-7","article-title":"DAMP-sensing receptors in sterile inflammation and inflammatory diseases","volume":"20","author":"Gong","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nri1391","article-title":"Toll-like receptor signalling","volume":"4","author":"Akira","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen Recognition and Innate Immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-pathmechdis-012419-032847","article-title":"DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation","volume":"15","author":"Zindel","year":"2020","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_19","first-page":"1","article-title":"Toll-like receptors activation, signaling, and targeting: An overview","volume":"43","author":"Sibaii","year":"2019","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.3389\/fimmu.2019.02536","article-title":"DAMPs and NETs in Sepsis","volume":"10","author":"Denning","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.arr.2017.02.004","article-title":"Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation","volume":"36","author":"Rahimifard","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Muhammad, T., Ikram, M., Ullah, R., Rehman, S.U., and Kim, M.O.J.N. (2019). Hesperetin, a citrus flavonoid, attenuates LPS-induced neuroinflammation, apoptosis and memory impairments by modulating TLR4\/NF-\u03baB signaling. Nutrients, 11.","DOI":"10.3390\/nu11030648"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/S0968-0004(02)02145-X","article-title":"A universal role for MyD88 in TLR\/IL-1R-mediated signaling","volume":"27","author":"Janssens","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Choi, S. (2012). MyD88, Myeloid Differentiation Primary Response Gene 88. Encyclopedia of Signaling Molecules, Springer.","DOI":"10.1007\/978-1-4419-0461-4_100875"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.intimp.2018.01.002","article-title":"Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice via inhibiting HMGB1 release and down-regulating TLR4\/MyD88 pathway","volume":"56","author":"Cheng","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fimmu.2014.00316","article-title":"A Comparative Review of Toll-Like Receptor 4 Expression and Functionality in Different Animal Species","volume":"5","author":"Vaure","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","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_29","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1080\/00207454.2019.1709845","article-title":"Toll-like receptor-4 pathway as a possible molecular mechanism for brain injuries after subarachnoid hemorrhage","volume":"130","author":"Wang","year":"2020","journal-title":"Int. J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5028","DOI":"10.3390\/ijms16035028","article-title":"Methemoglobin Is an Endogenous Toll-Like Receptor 4 Ligand\u2014Relevance to Subarachnoid Hemorrhage","volume":"16","author":"Kwon","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/14728222.2020.1752182","article-title":"Targeting TLR4-dependent inflammation in post-hemorrhagic brain injury","volume":"24","author":"Karimy","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sok\u00f3\u0142, B., W\u0105sik, N., Jankowski, R., Ho\u0142ysz, M., Wi\u0119ckowska, B., and Jagodzi\u0144ski, P. (2016). Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157853"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/nm.4361","article-title":"Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus","volume":"23","author":"Karimy","year":"2017","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/35100529","article-title":"Toll-like receptors and innate immunity","volume":"1","author":"Medzhitov","year":"2001","journal-title":"Nat. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/nri3713","article-title":"Assembly and localization of Toll-like receptor signalling complexes","volume":"14","author":"Gay","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1742-2094-10-27","article-title":"Toll-like receptor 4 signaling in intracerebral hemorrhage-induced inflammation and injury","volume":"10","author":"Fang","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_37","first-page":"144","article-title":"Metabolism, Blockade of the MEK\/ERK Pathway with a Raf Inhibitor Prevents Activation of Pro-Inflammatory Mediators in Cerebral Arteries and Reduction in Cerebral Blood Flow after Subarachnoid Hemorrhage in a Rat Model","volume":"31","author":"Maddahi","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ana.22102","article-title":"Recombinant osteopontin in cerebral vasospasm after subarachnoid hemorrhage","volume":"68","author":"Suzuki","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_39","first-page":"730","article-title":"Role of progesterone in TLR4-MyD88-dependent signaling pathway in pre-eclampsia","volume":"33","author":"Zhu","year":"2013","journal-title":"Acta Acad. Med. Wuhan"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2011\/848309","article-title":"Progesterone Administration Modulates Cortical TLR4\/NF-\u03baB Signaling Pathway after Subarachnoid Hemorrhage in Male Rats","volume":"2011","author":"Wang","year":"2011","journal-title":"Mediat. Inflamm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15797","DOI":"10.1038\/s41598-017-16124-8","article-title":"Inhibition of myeloid differentiation primary response protein 88 provides neuroprotection in early brain injury following experimental subarachnoid hemorrhage","volume":"7","author":"Yan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/j.ymthe.2018.05.019","article-title":"TLR4-binding DNA aptamers show a protective effect against acute stroke in animal models","volume":"26","author":"Moraga","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_43","first-page":"819","article-title":"TRAF6 is functional in inhibition of TLR4-mediated NF-\u03baB activation by resveratrol","volume":"24","author":"Jakus","year":"2013","journal-title":"J. Nutr. Chem."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"1960106","DOI":"10.1155\/2018\/1960106","article-title":"Biochanin A Reduces Inflammatory Injury and Neuronal Apoptosis following Subarachnoid Hemorrhage via Suppression of the TLRs\/TIRAP\/MyD88\/NF-kappaB Pathway","volume":"2018","author":"Wu","year":"2018","journal-title":"Behav. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zhang, X.-S., Li, W., Wu, Q., Wu, L.-Y., Ye, Z.-N., Liu, J.-P., Zhuang, Z., Zhou, M.-L., Zhang, X., and Hang, C.-H. (2016). Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081331"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/cns.12194","article-title":"Resveratrol attenuates early brain injury after subarachnoid hemorrhage through inhibition of NF-\u03baB-dependent inflammatory\/MMP-9 pathway","volume":"20","author":"Shao","year":"2014","journal-title":"CNS Neurosci. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e12525","DOI":"10.1111\/jpi.12525","article-title":"Melatonin and inflammation-Story of a double-edged blade","volume":"65","author":"Hardeland","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-019-1556-7","article-title":"Melatonin as a master regulator of cell death and inflammation: Molecular mechanisms and clinical implications for newborn care","volume":"10","author":"Tarocco","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.2174\/0929867324666170209104926","article-title":"Targeting Melatonin MT2 Receptors: A Novel Pharmacological Avenue for Inflammatory and Neuropathic Pain","volume":"25","author":"Posa","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/jpi.12087","article-title":"Melatonin alleviates secondary brain damage and neurobehavioral dysfunction after experimental subarachnoid hemorrhage: Possible involvement of TLR4-mediated inflammatory pathway","volume":"55","author":"Wang","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"378","DOI":"10.2174\/156720507781788873","article-title":"TNF-\u03b1 Inhibition as a Treatment Strategy for Neurodegenerative Disorders: New Drug Candidates and Targets","volume":"4","author":"Tweedie","year":"2007","journal-title":"Curr. Alzheimer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s11064-016-2129-0","article-title":"Pentoxifylline Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats: Possibly via Inhibiting TLR 4\/NF-\u03baB Signaling Pathway","volume":"42","author":"Xia","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1096\/fj.201800642RR","article-title":"Astaxanthin mitigates subarachnoid hemorrhage injury primarily by increasing sirtuin 1 and inhibiting the Toll-like receptor 4 signaling pathway","volume":"33","author":"Zhang","year":"2018","journal-title":"FASEB J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1186\/s12974-018-1388-x","article-title":"Fluoxetine attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage: A possible role for the regulation of TLR4\/MyD88\/NF-kappaB signaling pathway","volume":"15","author":"Liu","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","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_57","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4103\/1673-5374.200795","article-title":"Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage","volume":"12","author":"Suzuki","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/sj.mp.4002122","article-title":"MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation","volume":"13","author":"Gosselin","year":"2008","journal-title":"Mol. Psychiatry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-019-1561-x","article-title":"Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT\/STAT3 signaling","volume":"16","author":"Ryu","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep14246","article-title":"Discovery of small molecule inhibitors of MyD88-dependent signaling pathways using a computational screen","volume":"5","author":"Olson","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez-P\u00e9rez, S., Hern\u00e1ndez-Palma, L.A., Oregon-Romero, E., Anaya-Mac\u00edas, B.U., Garc\u00eda-Arellano, S., Gonz\u00e1lez-Estevez, G., and Mu\u00f1oz-Valle, J.F. (2020). Downregulation of Inflammatory Cytokine Release from IL-1\u03b2 and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor. Molecules, 25.","DOI":"10.3390\/molecules25184322"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"21096","DOI":"10.1074\/jbc.272.34.21096","article-title":"Novel Inhibitors of Cytokine-induced I\u03baB\u03b1 Phosphorylation and Endothelial Cell Adhesion Molecule Expression Show Anti-inflammatory Effects in Vivo","volume":"272","author":"Pierce","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6624","DOI":"10.1007\/s12035-016-0178-7","article-title":"Effects of Toll-Like Receptor 4 Antagonists Against Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage in Mice","volume":"54","author":"Kawakita","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-019-1538-9","article-title":"Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4\/NF-kB pathway","volume":"16","author":"Zusso","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1128\/AAC.47.10.3104-3108.2003","article-title":"Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy","volume":"47","author":"Pea","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3389\/fneur.2018.00097","article-title":"Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?","volume":"9","author":"Khattar","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hayman, E.G., Patel, A.P., James, R.F., and Simard, J.M. (2017). Heparin and Heparin-Derivatives in Post-Subarachnoid Hemorrhage Brain Injury: A Multimodal Therapy for a Multimodal Disease. Molecules, 22.","DOI":"10.3390\/molecules22050724"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3109\/01902148.2015.1091053","article-title":"Heparin and LPS-induced COX-2 expression in airway cells: A link between its anti-inflammatory effects and GAG sulfation","volume":"41","author":"Yi","year":"2015","journal-title":"Exp. Lung Res."},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1089\/scd.2019.0219","article-title":"Recent Advances in Stem Cell Research in Subarachnoid Hemorrhage","volume":"29","author":"Song","year":"2020","journal-title":"Stem Cells Dev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.bbi.2018.11.010","article-title":"Removal of microglial-specific MyD88 signaling alters dentate gyrus doublecortin and enhances opioid addiction-like behaviors","volume":"76","author":"Rivera","year":"2019","journal-title":"Brain Behav. Immun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4185\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:22Z","timestamp":1760161762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,18]]},"references-count":71,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22084185"],"URL":"https:\/\/doi.org\/10.3390\/ijms22084185","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,18]]}}}