{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:29:48Z","timestamp":1792074588475,"version":"4.4.0"},"reference-count":76,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","award":["ARUK-NCG2018A-002"],"award-info":[{"award-number":["ARUK-NCG2018A-002"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ARUK Senior Fellowship award","award":["ARUK-SRF-2019A-001"],"award-info":[{"award-number":["ARUK-SRF-2019A-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We studied the effects of systemic infection on brain cytokine level and cerebral vascular function in Alzheimer\u2019s disease and vascular dementia, in superior temporal cortex (Brodmann area 22) from Alzheimer\u2019s disease patients (n\u2009=\u200975), vascular dementia patients (n\u2009=\u200922) and age-matched control subjects (n\u2009=\u200946), stratified according to the presence or absence of terminal systemic infection. Brain cytokine levels were measured using Mesoscale Discovery Multiplex Assays and markers of cerebrovascular function were assessed by ELISA. Multiple brain cytokines were elevated in Alzheimer\u2019s disease and vascular dementia: IL-15 and IL-17A were maximally elevated in end-stage Alzheimer\u2019s disease (Braak tangle stage V\u2013VI) whereas IL-2, IL-5, IL12p40 and IL-16 were highest in intermediate Braak tangle stage III\u2013IV disease. Several cytokines (IL-1\u03b2, IL-6, TNF-\u03b1, IL-8 and IL-15) were further raised in Alzheimer\u2019s disease with systemic infection. Cerebral hypoperfusion\u2014indicated by decreased MAG:PLP1 and increased vascular endothelial growth factor-A (VEGF)\u2014and blood\u2013brain barrier leakiness, indicated by raised levels of fibrinogen, were exacerbated in Alzheimer\u2019s disease and vascular dementia patients, and also in non-dementia controls, with systemic infection. Amyloid-\u03b242 level did not vary with infection or in association with brain cytokine levels. In controls, cortical perfusion declined with increasing IFN-\u03b3, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and tumour necrosis factor-\u03b1 (TNF-\u03b1) but these relationships were lost with progression of Alzheimer\u2019s disease, and with infection (even in Braak stage 0\u2013II brains). Cortical platelet-derived growth factor receptor-\u03b2 (PDGFR\u03b2), a pericyte marker, was reduced, and endothelin-1 (EDN1) level was increased in Alzheimer\u2019s disease; these were related to amyloid-\u03b2 level and disease progression and only modestly affected by systemic infection. Our findings indicate that systemic infection alters brain cytokine levels and exacerbates cerebral hypoperfusion and blood\u2013brain barrier leakiness associated with Alzheimer\u2019s disease and vascular dementia, independently of the level of insoluble amyloid-\u03b2, and highlight systemic infection as an important contributor to dementia, requiring early identification and treatment in the elderly population.<\/jats:p>","DOI":"10.1093\/brain\/awab094","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T20:10:47Z","timestamp":1615493447000},"page":"1869-1883","source":"Crossref","is-referenced-by-count":76,"title":["Systemic infection exacerbates cerebrovascular dysfunction in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-8347","authenticated-orcid":false,"given":"Daniel","family":"Asby","sequence":"first","affiliation":[{"name":"Dementia Research Group, Bristol Medical School, University of Bristol, Bristol BS2 8DZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-130X","authenticated-orcid":false,"given":"Delphine","family":"Boche","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton S017 1BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9646-4456","authenticated-orcid":false,"given":"Stuart","family":"Allan","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, AV Hill Building, Manchester, M13 9PT, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group and University of Manchester, Manchester, M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Love","sequence":"additional","affiliation":[{"name":"Dementia Research Group, Bristol Medical School, University of Bristol, Bristol BS2 8DZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8594-1640","authenticated-orcid":false,"given":"J Scott","family":"Miners","sequence":"additional","affiliation":[{"name":"Dementia Research Group, Bristol Medical School, University of Bristol, Bristol BS2 8DZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"issue":"4","key":"2021072911404735500_awab094-B1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.biopsych.2008.07.024","article-title":"Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease","volume":"65","author":"Cunningham","year":"2009","journal-title":"Biol Psychiatry"},{"issue":"4","key":"2021072911404735500_awab094-B2","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.bbi.2006.12.007","article-title":"The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C)","volume":"21","author":"Cunningham","year":"2007","journal-title":"Brain Behav Immun"},{"issue":"16","key":"2021072911404735500_awab094-B3","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1001\/jama.2010.1553","article-title":"Long-term cognitive impairment and functional disability among survivors of severe sepsis","volume":"304","author":"Iwashyna","year":"2010","journal-title":"JAMA"},{"issue":"4","key":"2021072911404735500_awab094-B4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3233\/JAD-2008-13403","article-title":"Chlamydophila pneumoniae and the etiology of late-onset Alzheimer's disease","volume":"13","author":"Balin","year":"2008","journal-title":"J Alzheimers Dis"},{"issue":"12","key":"2021072911404735500_awab094-B5","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1111\/ene.12477","article-title":"A study on the association between infectious burden and Alzheimer's disease","volume":"22","author":"Bu","year":"2015","journal-title":"Eur J Neurol"},{"issue":"6","key":"2021072911404735500_awab094-B6","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1136\/jnnp.74.6.788","article-title":"Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease","volume":"74","author":"Holmes","year":"2003","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"10","key":"2021072911404735500_awab094-B7","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1212\/WNL.0b013e3181b6bb95","article-title":"Systemic inflammation and disease progression in Alzheimer disease","volume":"73","author":"Holmes","year":"2009","journal-title":"Neurology"},{"issue":"1","key":"2021072911404735500_awab094-B8","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/s13054-017-1850-7","article-title":"Translational evidence for two distinct patterns of neuroaxonal injury in sepsis: A longitudinal, prospective translational study","volume":"21","author":"Ehler","year":"2017","journal-title":"Crit Care"},{"issue":"1","key":"2021072911404735500_awab094-B9","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1074\/jbc.M117.786756","article-title":"Receptor for advanced glycation end products mediates sepsis-triggered amyloid-beta accumulation, Tau phosphorylation, and cognitive impairment","volume":"293","author":"Gasparotto","year":"2018","journal-title":"J Biol Chem"},{"key":"2021072911404735500_awab094-B10","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/1742-2094-9-146","article-title":"Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia","volume":"9","author":"Puntener","year":"2012","journal-title":"J Neuroinflammation"},{"issue":"2","key":"2021072911404735500_awab094-B11","first-page":"86","article-title":"Lipopolysaccharide endotoxemia induces amyloid-beta and p-tau formation in the rat brain","volume":"8","author":"Wang","year":"2018","journal-title":"Am J Nucl Med Mol Imaging"},{"key":"2021072911404735500_awab094-B12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1742-2094-4-4","article-title":"Microglia activation in sepsis: A case-control study","volume":"4","author":"Lemstra","year":"2007","journal-title":"J Neuroinflammation"},{"issue":"1","key":"2021072911404735500_awab094-B13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1750-3639.2004.tb00494.x","article-title":"The neuropathology of septic shock","volume":"14","author":"Sharshar","year":"2004","journal-title":"Brain Pathol"},{"issue":"4","key":"2021072911404735500_awab094-B14","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00401-003-0815-x","article-title":"Activation of vascular endothelial cells and perivascular cells by systemic inflammation-an immunohistochemical study of postmortem human brain tissues","volume":"107","author":"Uchikado","year":"2004","journal-title":"Acta Neuropathol"},{"issue":"1","key":"2021072911404735500_awab094-B15","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s40478-018-0592-3","article-title":"Systemic infection modifies the neuroinflammatory response in late stage Alzheimer's disease","volume":"6","author":"Rakic","year":"2018","journal-title":"Acta Neuropathol Commun"},{"issue":"10","key":"2021072911404735500_awab094-B16","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/s41593-018-0234-x","article-title":"The role of brain vasculature in neurodegenerative disorders","volume":"21","author":"Sweeney","year":"2018","journal-title":"Nat Neurosci"},{"issue":"1","key":"2021072911404735500_awab094-B17","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jalz.2018.07.222","article-title":"Vascular dysfunction-The disregarded partner of Alzheimer's disease","volume":"15","author":"Sweeney","year":"2019","journal-title":"Alzheimers Dement"},{"key":"2021072911404735500_awab094-B18","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12916-014-0206-2","article-title":"The overlap between vascular disease and Alzheimer's disease\u2013lessons from pathology","volume":"12","author":"Attems","year":"2014","journal-title":"BMC Med"},{"issue":"2","key":"2021072911404735500_awab094-B19","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-brain barrier breakdown in the aging human hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"issue":"2","key":"2021072911404735500_awab094-B20","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat Med"},{"issue":"47","key":"2021072911404735500_awab094-B21","doi-asserted-by":"crossref","first-page":"E4502","DOI":"10.1073\/pnas.1317918110","article-title":"Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease","volume":"110","author":"Benzinger","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021072911404735500_awab094-B22","doi-asserted-by":"crossref","first-page":"11934","DOI":"10.1038\/ncomms11934","article-title":"Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis","volume":"7","author":"Iturria-Medina","year":"2016","journal-title":"Nat Commun"},{"issue":"3","key":"2021072911404735500_awab094-B23","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1161\/STROKEAHA.119.028814","article-title":"APOE4 accelerates development of dementia after stroke: Is there a role for cerebrovascular dysfunction?","volume":"51","author":"Montagne","year":"2020","journal-title":"Stroke"},{"issue":"4","key":"2021072911404735500_awab094-B24","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/bpa.12331","article-title":"Pathophysiology of hypoperfusion of the precuneus in early Alzheimer's disease","volume":"26","author":"Miners","year":"2016","journal-title":"Brain Pathol"},{"issue":"Pt 4","key":"2021072911404735500_awab094-B25","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1093\/brain\/awv025","article-title":"Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer's disease and vascular dementia","volume":"138","author":"Thomas","year":"2015","journal-title":"Brain"},{"issue":"Pt 5","key":"2021072911404735500_awab094-B26","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1093\/brain\/awu040","article-title":"Pathophysiology of white matter perfusion in Alzheimer's disease and vascular dementia","volume":"137","author":"Barker","year":"2014","journal-title":"Brain"},{"issue":"7","key":"2021072911404735500_awab094-B27","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/jcbfm.2013.46","article-title":"Assessing white matter ischemic damage in dementia patients by measurement of myelin proteins","volume":"33","author":"Barker","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"2021072911404735500_awab094-B28","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1177\/0271678X17690761","article-title":"Differing associations between Abeta accumulation, hypoperfusion, blood-brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease","volume":"38","author":"Miners","year":"2018","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"2021072911404735500_awab094-B29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/00006676-200301000-00010","article-title":"Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer","volume":"26","author":"Buchler","year":"2003","journal-title":"Pancreas"},{"issue":"4","key":"2021072911404735500_awab094-B30","doi-asserted-by":"crossref","first-page":"853","DOI":"10.3233\/JAD-2012-111760","article-title":"Endothelin-1 is elevated in Alzheimer's disease and upregulated by amyloid-beta","volume":"29","author":"Palmer","year":"2012","journal-title":"J Alzheimers Dis"},{"issue":"3","key":"2021072911404735500_awab094-B31","doi-asserted-by":"crossref","first-page":"577","DOI":"10.3233\/JAD-130383","article-title":"Endothelin-converting enzyme-1 activity, endothelin-1 production, and free radical-dependent vasoconstriction in Alzheimer's disease","volume":"36","author":"Palmer","year":"2013","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"2021072911404735500_awab094-B32","first-page":"41","article-title":"Infectious and coronary artery disease","volume":"12","author":"Rezaee-Zavareh","year":"2016","journal-title":"ARYA Atheroscler"},{"issue":"3","key":"2021072911404735500_awab094-B33","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1161\/01.CIR.101.3.252","article-title":"Infections, inflammation, and the risk of coronary heart disease","volume":"101","author":"Roivainen","year":"2000","journal-title":"Circulation"},{"issue":"18","key":"2021072911404735500_awab094-B34","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1161\/CIRCULATIONAHA.109.918417","article-title":"Inflammation in peripheral artery disease","volume":"122","author":"Brevetti","year":"2010","journal-title":"Circulation"},{"issue":"9","key":"2021072911404735500_awab094-B35","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/ATVBAHA.108.179705","article-title":"Inflammation in atherosclerosis","volume":"32","author":"Libby","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"2021072911404735500_awab094-B36","first-page":"3","article-title":"Association between bacterial infection and peripheral vascular disease: A review","volume":"25","author":"Budzy\u0144ski","year":"2016","journal-title":"Int J Angiol"},{"issue":"1","key":"2021072911404735500_awab094-B37","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1473-3099(01)00168-2","article-title":"Evidence for infectious agents in cardiovascular disease and atherosclerosis","volume":"2","author":"Leinonen","year":"2002","journal-title":"Lancet Infect Dis"},{"issue":"10","key":"2021072911404735500_awab094-B38","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.7150\/ijbs.7502","article-title":"The vascular endothelium and human diseases","volume":"9","author":"Rajendran","year":"2013","journal-title":"Int J Biol Sci"},{"issue":"1","key":"2021072911404735500_awab094-B39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2007.11.002","article-title":"Endothelial dysfunction: A key to the pathophysiology and natural history of peripheral arterial disease?","volume":"197","author":"Brevetti","year":"2008","journal-title":"Atherosclerosis"},{"issue":"2 Suppl 41","key":"2021072911404735500_awab094-B40","first-page":"S71","article-title":"Vasculitides secondary to infections","volume":"24","author":"Pagnoux","year":"2006","journal-title":"Clin Exp Rheumatol"},{"issue":"8","key":"2021072911404735500_awab094-B41","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1161\/01.CIR.0000051456.68470.C8","article-title":"Oral health and peripheral arterial disease","volume":"107","author":"Hung","year":"2003","journal-title":"Circulation"},{"issue":"1","key":"2021072911404735500_awab094-B42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","article-title":"National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: A practical approach","volume":"123","author":"Montine","year":"2012","journal-title":"Acta Neuropathol"},{"issue":"3","key":"2021072911404735500_awab094-B43","doi-asserted-by":"crossref","first-page":"E396","DOI":"10.1073\/pnas.1612930114","article-title":"Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity","volume":"114","author":"Li","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"2021072911404735500_awab094-B44","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.4049\/jimmunol.1002188","article-title":"Contribution of astrocyte-derived IL-15 to CD8 T cell effector functions in multiple sclerosis","volume":"185","author":"Saikali","year":"2010","journal-title":"J Immunol"},{"issue":"9","key":"2021072911404735500_awab094-B45","doi-asserted-by":"crossref","first-page":"e867","DOI":"10.1212\/WNL.0000000000006082","article-title":"CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease","volume":"91","author":"Janelidze","year":"2018","journal-title":"Neurology"},{"issue":"4","key":"2021072911404735500_awab094-B46","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1080\/09168451.2018.1562874","article-title":"LncRNA17A regulates autophagy and apoptosis of SH-SY5Y cell line as an in vitro model for Alzheimer's disease","volume":"83","author":"Wang","year":"2019","journal-title":"Biosci Biotechnol Biochem"},{"issue":"10","key":"2021072911404735500_awab094-B47","doi-asserted-by":"crossref","first-page":"e0141596","DOI":"10.1371\/journal.pone.0141596","article-title":"Interleukin17A promotes postoperative cognitive dysfunction by triggering beta-amyloid accumulation via the transforming growth factor-beta (TGFbeta)\/Smad signaling pathway","volume":"10","author":"Tian","year":"2015","journal-title":"PLoS One"},{"issue":"8","key":"2021072911404735500_awab094-B48","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nm.3913","article-title":"Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin","volume":"21","author":"Zenaro","year":"2015","journal-title":"Nat Med"},{"issue":"2","key":"2021072911404735500_awab094-B49","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/s41593-017-0059-z","article-title":"Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response","volume":"21","author":"Faraco","year":"2018","journal-title":"Nat Neurosci"},{"issue":"3","key":"2021072911404735500_awab094-B50","first-page":"792","article-title":"An early and late peak in microglial activation in Alzheimer's disease trajectory","volume":"140","author":"Fan","year":"2017","journal-title":"Brain"},{"issue":"6","key":"2021072911404735500_awab094-B51","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1093\/brain\/awy079","article-title":"Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer's disease","volume":"141","author":"Hamelin","year":"2018","journal-title":"Brain"},{"issue":"6","key":"2021072911404735500_awab094-B52","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/bpa.12717","article-title":"The relationship between the morphological subtypes of microglia and Alzheimer's disease neuropathology","volume":"29","author":"Paasila","year":"2019","journal-title":"Brain Pathol"},{"issue":"1","key":"2021072911404735500_awab094-B53","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/jcbfm.2015.44","article-title":"Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease","volume":"36","author":"Halliday","year":"2016","journal-title":"J Cereb Blood Flow Metab"},{"key":"2021072911404735500_awab094-B54","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.neulet.2015.09.025","article-title":"Shedding of soluble platelet-derived growth factor receptor-beta from human brain pericytes","volume":"607","author":"Sagare","year":"2015","journal-title":"Neurosci Lett"},{"issue":"1","key":"2021072911404735500_awab094-B55","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13195-019-0534-8","article-title":"CSF evidence of pericyte damage in Alzheimer's disease is associated with markers of blood-brain barrier dysfunction and disease pathology","volume":"11","author":"Miners","year":"2019","journal-title":"Alzheimers Res Ther"},{"issue":"3","key":"2021072911404735500_awab094-B56","doi-asserted-by":"crossref","first-page":"H1016","DOI":"10.1152\/ajpheart.00779.2004","article-title":"Cytokines and vascular reactivity in resistance arteries","volume":"288","author":"Vila","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"11","key":"2021072911404735500_awab094-B57","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1161\/STROKEAHA.114.006613","article-title":"Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia","volume":"45","author":"Murray","year":"2014","journal-title":"Stroke"},{"key":"2021072911404735500_awab094-B58","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1742-2094-5-38","article-title":"Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism","volume":"5","author":"Semmler","year":"2008","journal-title":"J Neuroinflamm"},{"key":"2021072911404735500_awab094-B59","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.nbd.2018.12.018","article-title":"Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury","volume":"124","author":"Sankar","year":"2019","journal-title":"Neurobiol Dis"},{"issue":"5","key":"2021072911404735500_awab094-B60","doi-asserted-by":"crossref","first-page":"907","DOI":"10.3171\/jns.2003.99.5.0907","article-title":"Interleukin-1beta and adverse effects on cerebral blood flow during long-term global hypoperfusion","volume":"99","author":"Maher","year":"2003","journal-title":"J Neurosurg"},{"issue":"4 Pt 1","key":"2021072911404735500_awab094-B61","doi-asserted-by":"crossref","first-page":"C854","DOI":"10.1152\/ajpcell.1992.262.4.C854","article-title":"Transcriptional regulation of the endothelin-1 gene by TNF-alpha","volume":"262","author":"Marsden","year":"1992","journal-title":"Am J Physiol"},{"key":"2021072911404735500_awab094-B62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2016.03.010","article-title":"The blood-brain barrier in systemic inflammation","volume":"60","author":"Varatharaj","year":"2017","journal-title":"Brain Behav Immun"},{"issue":"2","key":"2021072911404735500_awab094-B63","doi-asserted-by":"crossref","first-page":"C135","DOI":"10.1152\/ajpcell.00136.2018","article-title":"Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke","volume":"316","author":"Yang","year":"2019","journal-title":"Am J Physiol Cell Physiol"},{"issue":"4","key":"2021072911404735500_awab094-B64","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1042\/BST20140319","article-title":"The blood-brain barrier endothelium: A target for pro-inflammatory cytokines","volume":"43","author":"Rochfort","year":"2015","journal-title":"Biochem Soc Trans"},{"issue":"8","key":"2021072911404735500_awab094-B65","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.4049\/jimmunol.177.8.5574","article-title":"IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program","volume":"177","author":"Argaw","year":"2006","journal-title":"J Immunol"},{"issue":"21","key":"2021072911404735500_awab094-B66","doi-asserted-by":"crossref","first-page":"8153","DOI":"10.1523\/JNEUROSCI.20-21-08153.2000","article-title":"Interleukin-1beta-induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: A magnetic resonance study","volume":"20","author":"Blamire","year":"2000","journal-title":"J Neurosci"},{"issue":"10","key":"2021072911404735500_awab094-B67","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/0024-3205(95)00008-T","article-title":"Systemic cytokine administration can affect blood-brain barrier permeability in the rat","volume":"56","author":"Saija","year":"1995","journal-title":"Life Sci"},{"issue":"1","key":"2021072911404735500_awab094-B68","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0165-5728(95)00148-4","article-title":"The influence of cytokines on the integrity of the blood-brain barrier in vitro","volume":"64","author":"de Vries","year":"1996","journal-title":"J Neuroimmunol"},{"issue":"5","key":"2021072911404735500_awab094-B69","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1159\/000350470","article-title":"Effects of interleukin-6 on the expression of tight junction proteins in isolated cerebral microvessels from yearling and adult sheep","volume":"20","author":"Cohen","year":"2013","journal-title":"Neuroimmunomodulation"},{"issue":"7","key":"2021072911404735500_awab094-B70","doi-asserted-by":"crossref","first-page":"e101815","DOI":"10.1371\/journal.pone.0101815","article-title":"Downregulation of blood-brain barrier phenotype by proinflammatory cytokines involves NADPH oxidase-dependent ROS generation: Consequences for interendothelial adherens and tight junctions","volume":"9","author":"Rochfort","year":"2014","journal-title":"PLoS One"},{"issue":"3","key":"2021072911404735500_awab094-B71","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/jnc.13408","article-title":"Tumour necrosis factor-alpha-mediated disruption of cerebrovascular endothelial barrier integrity in vitro involves the production of proinflammatory interleukin-6","volume":"136","author":"Rochfort","year":"2016","journal-title":"J Neurochem"},{"key":"2021072911404735500_awab094-B72","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/1742-2094-8-106","article-title":"Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-alpha, releasing matrix metalloproteinase-9 and migrating in vitro","volume":"8","author":"Takata","year":"2011","journal-title":"J Neuroinflamm"},{"issue":"10","key":"2021072911404735500_awab094-B73","doi-asserted-by":"crossref","first-page":"e110024","DOI":"10.1371\/journal.pone.0110024","article-title":"Interleukin-1beta induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes","volume":"9","author":"Wang","year":"2014","journal-title":"PLoS One"},{"key":"2021072911404735500_awab094-B74","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jneuroim.2019.04.011","article-title":"IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis","volume":"332","author":"Setiadi","year":"2019","journal-title":"J Neuroimmunol"},{"issue":"6","key":"2021072911404735500_awab094-B75","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1182\/blood-2018-07-818211","article-title":"The multifaceted role of fibrinogen in tissue injury and inflammation","volume":"133","author":"Luyendyk","year":"2019","journal-title":"Blood"},{"issue":"6","key":"2021072911404735500_awab094-B76","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/rheumatology\/40.6.640","article-title":"Cardiovascular risk factors, including thrombotic variables, in a population with rheumatoid arthritis","volume":"40","author":"McEntegart","year":"2001","journal-title":"Rheumatology (Oxford)"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awab094\/38684670\/awab094.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/144\/6\/1869\/39427639\/awab094.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/144\/6\/1869\/39427639\/awab094.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T11:45:52Z","timestamp":1627559152000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/144\/6\/1869\/6173392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":76,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3,16]]},"published-print":{"date-parts":[[2021,7,28]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awab094","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6,1]]},"published":{"date-parts":[[2021,3,16]]}}}