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To clarify the mechanism of IGF-1 transport at the blood\u2013cerebrospinal fluid (CSF) barrier of the immature brain, we combined studies of in vivo preterm piglet and rabbit models with an in vitro transwell cell culture model of neonatal primary murine choroid plexus epithelial (ChPE) cells. We identified IGF-1-positive intracellular vesicles in ChPE cells and provided data indicating a directional transport of IGF-1 from the basolateral to the apical media in extracellular vesicles (EVs). Exposure of the ChPE cells to human IGF-1 on the basolateral side increased the secretion of IGF-1-positive EVs in the apical media. Mass spectrometry analysis displayed similarities in protein content between EVs derived from preterm piglet CSF-derived and ChPE cell\u2013derived EVs. Furthermore, exposure of ChPE cells to human IGF-1 caused an enrichment of human IGF-1 and transmembrane p24 trafficking protein 2, proteins important for perinatal development, in apical media\u2013derived EVs. Moreover, intraventricular injections of ChPE cell\u2013derived EVs in preterm rabbit pups resulted in an uptake of EVs in the brain, displaying penetration through the ependymal lining and deep into the hippocampus. Finally, exposure of rat hippocampus neurons to ChPE cell\u2013derived EVs resulted in internalization of the EVs in hippocampal soma and neurites. In summary, we describe a transport pathway for blood-borne IGF-1 in EVs through the blood\u2013CSF barrier to the hippocampus in the immature brain.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgae496","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T11:02:12Z","timestamp":1731409332000},"source":"Crossref","is-referenced-by-count":9,"title":["Choroid plexus extracellular vesicle transport of blood-borne insulin-like growth factor 1 to the hippocampus of the immature brain"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9755-1755","authenticated-orcid":false,"given":"Niklas","family":"Ortenl\u00f6f","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund, Pediatrics, Lund University , 22184 Lund ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvi","family":"Vallius","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, 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