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Neurosci."],"abstract":"<jats:p>Background: Diabetic encephalopathy is a prevalent complication of diabetes mellitus, which is primarily characterized by hippocampal injury and blood-brain barrier (BBB) dysfunction. This study investigates the neuroprotective effect of tea polyphenols (TP) on hippocampal tissue in early-stage diabetic mice. Methods: Sixty BALB\/c mice were randomly assigned to the control group (C), the diabetes group (T0), and the TP-treated group (T1). After successful model induction, mice in group T1 received TP intragastrically (100 mg\/kg\/d). Hematoxylin and eosin (H&amp;E), toluidine blue, and Hoechst 33342 staining, combined with polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), were used to assess the effects of TP on hippocampal histology, inflammation and oxidative stress, the advanced glycation end products (AGEs) \u2013 Receptor for Advanced Glycation End products (RAGE) pathway, and the expression of key proteins associated with the BBB. Results: The contents of AGEs, RAGE, NF-\u03baB, P-glycoprotein (P38), and oxidative stress factors in group T1 were lower than those in group T0 at 7, 14, and 21 days (p &lt; 0.05). At the same time points, the mRNA expression levels of inflammatory factors in group T1 were lower than those in group T0 (p &lt; 0.05). Moreover, compared with group T0, both P-glycoprotein (P-gp) protein expression and glucose transporters (Glut1) mRNA expression increased in group T1 (p &lt; 0.05). The mRNA expression levels of key BBB-related molecules in group T1 also increased to varying degrees (p &lt; 0.05). Histopathological analysis showed marked improvement in the hippocampal architecture of group T1 compared with group T0. Moreover, the expression levels of P38, NF-\u03baB, IL-6, TNF-\u03b1, ROS, and Glut1 were significantly or highly significantly positively correlated with RAGE protein levels (p &lt; 0.05 or p &lt; 0.01). Conclusions: TP enhanced BBB structural integrity by inhibiting the AGEs\u2013RAGE pathway, thereby attenuating hippocampal tissue damage.<\/jats:p>","DOI":"10.31083\/jin49065","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T08:26:51Z","timestamp":1780129611000},"source":"Crossref","is-referenced-by-count":0,"title":["Tea Polyphenols Protect the Blood\u2013Brain Barrier Structure in the Hippocampus of Early Diabetic Mice by Inhibiting the AGEs\u2013RAGE Pathway"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2348-7902","authenticated-orcid":true,"given":"Zhiyong","family":"Xu","sequence":"first","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, 453003 Xinxiang, Henan, China"},{"name":"Henan International Joint Laboratory of Animal Health Breeding and Disease Prevention and Control, Henan Institute of Science and Technology, 453003 Xinxiang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4777-9491","authenticated-orcid":true,"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Emergency Department, The 83rd Army Group Hospital of the Chinese People\u2019s Liberation Army, 453003 Xinxiang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-8116","authenticated-orcid":true,"given":"Yan","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, 453003 Xinxiang, Henan, China"},{"name":"Henan International Joint Laboratory of Animal Health Breeding and Disease Prevention and Control, Henan Institute of Science and Technology, 453003 Xinxiang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Ziegler D, Porta M, Papanas N, Mota M, Jermendy G, Beltramo E, et al. 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