{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:19:25Z","timestamp":1785442765100,"version":"3.56.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016905","name":"Hugh Green Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016905","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001543","name":"Neurological Foundation of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Pericytes in the central nervous system are essential for maintaining blood-brain barrier function, regulating blood flow, modulating immune responses, and interacting closely with surrounding cells of the neurovascular unit to support brain homeostasis. Increasing evidence has highlighted their involvement in age-related neuroinflammation, where their dysfunction may contribute to sustained inflammatory states associated with neurodegenerative disorders. Here, we compared inflammatory responses to lipopolysaccharide (LPS) in primary cerebral pericytes from neonatal and adult mice and adult humans. Our findings indicate that neonatal mouse pericytes display heightened inflammatory activation, with elevated levels of ICAM-1 and several cytokines, compared to adult mouse pericytes reflecting a more reactive phenotype. In contrast, adult mouse pericytes exhibited a significantly reduced cytokine release profile, suggesting lower responsiveness. Notably, while cytokine secretion patterns in adult human pericytes, in part, mirrored those in neonatal mouse pericytes, nitric oxide production, which was observed in mouse pericytes, was absent in the human cells. These results underscore species- and age-dependent variations in cellular behavior, emphasizing the importance of utilizing human brain cell systems when conducting research on neuroinflammation. Understanding these distinctions is vital for designing accurate studies and developing targeted therapies for neuroinflammatory conditions.<\/jats:p>","DOI":"10.1186\/s13041-025-01209-7","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T10:25:11Z","timestamp":1744971911000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Heterogeneity in pericyte inflammatory responses across age and species highlight the importance of human cell models"],"prefix":"10.1186","volume":"18","author":[{"given":"Taylor J.","family":"Stevenson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M.","family":"Montgomery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Y.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dragunow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"1209_CR1","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nn.4288","volume":"19","author":"MD Sweeney","year":"2016","unstructured":"Sweeney MD, Ayyadurai S, Zlokovic BV. Pericytes of the neurovascular unit: key functions and signaling pathways. Nat Neurosci. 2016;19:771\u201383.","journal-title":"Nat Neurosci"},{"key":"1209_CR2","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/1742-2094-11-104","volume":"11","author":"D Jansson","year":"2014","unstructured":"Jansson D, Rustenhoven J, Feng S, Hurley D, Oldfield RL, Bergin PS, Mee EW, Faull RL, Dragunow M. A role for human brain pericytes in neuroinflammation. J Neuroinflammation. 2014;11:104.","journal-title":"J Neuroinflammation"},{"key":"1209_CR3","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.tips.2016.12.001","volume":"38","author":"J Rustenhoven","year":"2017","unstructured":"Rustenhoven J, Jansson D, Smyth LC, Dragunow M. Brain pericytes as mediators of neuroinflammation. Trends Pharmacol Sci. 2017;38:291\u2013304.","journal-title":"Trends Pharmacol Sci"},{"key":"1209_CR4","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1038\/nn.2946","volume":"14","author":"EA Winkler","year":"2011","unstructured":"Winkler EA, Bell RD, Zlokovic B. V. Central nervous system pericytes in health and disease. Nat Neurosci. 2011;14:1398\u2013405.","journal-title":"Nat Neurosci"},{"key":"1209_CR5","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1038\/s41380-022-01511-z","volume":"27","author":"EG Knox","year":"2022","unstructured":"Knox EG, Aburto MR, Clarke G, Cryan JF, O\u2019Driscoll CM. The blood-brain barrier in aging and neurodegeneration. Mol Psychiatry. 2022;27:2659\u201373.","journal-title":"Mol Psychiatry"},{"key":"1209_CR6","doi-asserted-by":"crossref","unstructured":"T\u00f6r\u00f6k O, Schreiner B, Schaffenrath J, Tsai H-C, Maheshwari U, Stifter SA, Welsh C, Amorim A, Sridhar S, Utz SG, Mildenberger W, Nassiri S, Delorenzi M, Aguzzi A, Han MH, Greter M, Becher B, Keller A. Pericytes regulate vascular immune homeostasis in the CNS. Proc. Natl. Acad. Sci. U.S.A. 118, e2016587118 (2021).","DOI":"10.1073\/pnas.2016587118"},{"key":"1209_CR7","doi-asserted-by":"crossref","unstructured":"Duan L, Zhang X-D, Miao W-Y, Sun Y-J, Xiong G, Wu Q, Li G, Yang P, Yu H, Li H, Wang Y, Zhang M, Hu L-Y, Tong X, Zhou W-H, Yu X. PDGFR\u03b2 Cells Rapidly Relay Inflammatory Signal from the Circulatory System to Neurons via Chemokine CCL2. Neuron 100, 183\u2013200.e8 (2018).","DOI":"10.1016\/j.neuron.2018.08.030"},{"key":"1209_CR8","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/1742-2094-8-139","volume":"8","author":"A Kovac","year":"2011","unstructured":"Kovac A, Erickson MA, Banks WA. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide. J Neuroinflammation. 2011;8:139.","journal-title":"J Neuroinflammation"},{"key":"1209_CR9","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/1742-2094-11-70","volume":"11","author":"LB Christensen","year":"2014","unstructured":"Christensen LB, Woods TA, Carmody AB, Caughey B, Peterson KE. Age-related differences in neuroinflammatory responses associated with a distinct profile of regulatory markers on neonatal microglia. 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Eur Heart J. 2012;33:829\u201337.","journal-title":"Eur Heart J"},{"key":"1209_CR17","doi-asserted-by":"publisher","first-page":"619230","DOI":"10.3389\/fphys.2020.619230","volume":"11","author":"RG Underly","year":"2021","unstructured":"Underly RG, Shih AY, Rapid. Nitric oxide Synthesis-Dependent activation of MMP-9 at pericyte Somata during capillary ischemia in vivo. Front Physiol. 2021;11:619230.","journal-title":"Front Physiol"},{"key":"1209_CR18","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s12974-018-1192-7","volume":"15","author":"A Rana","year":"2018","unstructured":"Rana A, Musto AE. The role of inflammation in the development of epilepsy. J Neuroinflammation. 2018;15:144.","journal-title":"J Neuroinflammation"}],"container-title":["Molecular Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-025-01209-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13041-025-01209-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-025-01209-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T10:25:17Z","timestamp":1744971917000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularbrain.biomedcentral.com\/articles\/10.1186\/s13041-025-01209-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,18]]},"references-count":18,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1209"],"URL":"https:\/\/doi.org\/10.1186\/s13041-025-01209-7","relation":{},"ISSN":["1756-6606"],"issn-type":[{"value":"1756-6606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,18]]},"assertion":[{"value":"13 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal and human work described in this study was approved by the University of Auckland Ethics Committee (AEC002344) and the Health and Disabilities Ethics Committee New Zealand (AKL\/88\/025\/AM2217), respectively.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors consent to publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37"}}