{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:39:14Z","timestamp":1790991554619,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"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>In diabetic peripheral neuropathy (DPN), metabolic disorder by hyperglycemia progresses in peripheral nerves. In addition to the direct damage to peripheral neural axons, the homeostatic mechanism of peripheral nerves is disrupted by dysfunction of the blood\u2013nerve barrier (BNB) and Schwann cells. The disruption of the BNB, which is a crucial factor in DPN development and exacerbation, causes axonal degeneration via various pathways. Although many reports revealed that hyperglycemia and other important factors, such as dyslipidemia-induced dysfunction of Schwann cells, contributed to DPN, the molecular mechanisms underlying BNB disruption have not been sufficiently elucidated, mainly because of the lack of in vitro studies owing to difficulties in establishing human cell lines from vascular endothelial cells and pericytes that form the BNB. We have developed, for the first time, temperature-sensitive immortalized cell lines of vascular endothelial cells and pericytes originating from the BNB of human sciatic nerves, and we have elucidated the disruption to the BNB mainly in response to advanced glycation end products in DPN. Recently, we succeeded in developing an in vitro BNB model to reflect the anatomical characteristics of the BNB using cell sheet engineering, and we established immortalized cell lines originating from the human BNB. In this article, we review the pathologic evidence of the pathology of DPN in terms of BNB disruption, and we introduce the current in vitro BNB models.<\/jats:p>","DOI":"10.3390\/ijms22010062","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T08:38:43Z","timestamp":1608712723000},"page":"62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Blood\u2013Nerve Barrier (BNB) Pathology in Diabetic Peripheral Neuropathy and In Vitro Human BNB Model"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0314-550X","authenticated-orcid":false,"given":"Yukio","family":"Takeshita","sequence":"first","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Yamaguchi 753-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Yamaguchi 753-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Yamaguchi 753-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"IDF Diabetes Atlas Committee. 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