{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:45:18Z","timestamp":1792583118479,"version":"4.5.0"},"reference-count":176,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The blood\u2013brain barrier [BBB] is a highly specialized structure that regulates the influx and efflux of nutrients and metabolic waste to maintain homeostasis of the central nervous system. This selective permeability of the BBB is sustained by tight junctions that are supported by pericytes and astrocytes. Recently, extracellular vesicles have emerged as mediators of intercellular communication across and within the BBB. This review examines the bidirectional transport of EVs across the BBB and the distinct functional impacts of blood\u2010borne EVs. On the luminal side, circulating EVs derived from platelets, erythrocytes, and leukocytes convey systemic signals to the neurovasculature. Platelet\u2010derived EVs deliver growth factors and lipid mediators that promote vascular repair and modulate adaptive immunity during endothelial disruption. Erythrocyte\u2010derived EVs selectively shed surface markers like CD47 to regulate cellular turnover while simultaneously providing phosphatidylserine that maintains hemostasis and nitric oxide bioavailability. Meanwhile, leukocytic\u2010derived EVs protect and transport immunological cargo, such as MHC complexes and cytokines, functioning as critical sensors and amplifiers of immune surveillance at the vascular interface. Together, these circulating EV populations influence endothelial signaling, transporter expression, and tight junction integrity from the vascular side. Conversely, on the abluminal side, the roles of brain parenchymal\u2010derived EVs secreted by astrocytes, pericytes, neurons, and microglia are explored in regulating local neurovascular coupling, vascular tone, and endothelial responsiveness. Within this microenvironment, astrocyte\u2010derived EVs provide neurotrophic and neuroprotective support by delivering angiogenic factors and cytoprotective chaperone proteins like HSP70 to protect cells from mechanical and oxidative stress. Pericyte\u2010derived EVs preserve microvascular barrier integrity by transporting regulatory microRNAs and angiopoietin\u20101 to directly upregulate endothelial tight junction proteins. Furthermore, neuron\u2010derived EVs participate in activity\u2010dependent signaling, transferring vital microRNAs to endothelial cells to promote vascular stability and support synaptic plasticity. By framing the BBB as an active communication system, this review underscores how peripheral and central EVs integrate systemic and neural environments, highlighting their fundamental roles in BBB physiology and, beyond, their profound implications as biomarkers of CNS distress and programmable vehicles for targeted drug delivery.<\/jats:p>","DOI":"10.1111\/micc.70091","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:24:29Z","timestamp":1792581869000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tiny Travelers, Big Impact: Physiological Effects of Extracellular Vesicles on the Blood\u2010Brain Barrier"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1623-3947","authenticated-orcid":false,"given":"Linda","family":"Lin","sequence":"first","affiliation":[{"name":"Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2492-8062","authenticated-orcid":false,"given":"Manisha","family":"Patil","sequence":"additional","affiliation":[{"name":"Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5257-963X","authenticated-orcid":false,"given":"Simon","family":"Hawke","sequence":"additional","affiliation":[{"name":"Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"},{"name":"Central West Neurology and Neurosurgery  Orange New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6839-7628","authenticated-orcid":false,"given":"Felix","family":"Marsh\u2010Wakefield","sequence":"additional","affiliation":[{"name":"Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"},{"name":"Liver Injury and Cancer Program Centenary Institute  Sydney New South Wales Australia"},{"name":"Human Cancer and Viral Immunology Laboratory The University of Sydney  Sydney New South Wales Australia"},{"name":"Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0442-0462","authenticated-orcid":false,"given":"Georges E.","family":"Grau","sequence":"additional","affiliation":[{"name":"Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"},{"name":"Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2003.12.016","article-title":"The Blood\u2010Brain Barrier: An Overview: Structure, Regulation, and Clinical Implications","volume":"16","author":"Ballabh P.","year":"2004","journal-title":"Neurobiology of Disease"},{"issue":"14","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"9195","DOI":"10.1093\/nar\/gku594","article-title":"Activity\u2010Associated miRNA Are Packaged in Map1b\u2010Enriched Exosomes Released From Depolarized Neurons","volume":"42","author":"Goldie B. 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