PMID- 36609953 OWN - NLM STAT- MEDLINE DCOM- 20230501 LR - 20230501 IS - 1993-0402 (Electronic) IS - 1672-0415 (Linking) VI - 29 IP - 5 DP - 2023 May TI - Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways. PG - 448-458 LID - 10.1007/s11655-023-3592-5 [doi] AB - OBJECTIVE: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- beta (Abeta), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Abeta in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01). CONCLUSION: EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A beta deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways. CI - (c) 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Wang, Yuan AU - Wang Y AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Wang, Qiang AU - Wang Q AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Luo, Di AU - Luo D AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Zhao, Pu AU - Zhao P AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Zhong, Sha-Sha AU - Zhong SS AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Dai, Biao AU - Dai B AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Wang, Jia-Jyu AU - Wang JJ AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Wan, Yi-Tong AU - Wan YT AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Liu, Zhi-Bin AU - Liu ZB AD - College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China. FAU - Yang, Huan AU - Yang H AD - Department of Traditional Chinese Medicine, Baotou Medical College, Baotou, Inner Mongolia Autonomous Region, 014040, China. 102021027@btmc.edu.cn. LA - eng PT - Journal Article DEP - 20230107 PL - China TA - Chin J Integr Med JT - Chinese journal of integrative medicine JID - 101181180 RN - 53-59-8 (NADP) RN - 0 (Toll-Like Receptor 4) RN - 0 (HMGB1 Protein) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Amyloid beta-Peptides) RN - 0 (TLR4 protein, human) RN - 0 (Tlr4 protein, mouse) SB - IM MH - Mice MH - Humans MH - Animals MH - NADP/metabolism MH - Toll-Like Receptor 4 MH - *HMGB1 Protein/metabolism MH - Receptor for Advanced Glycation End Products/metabolism MH - Blood-Brain Barrier/metabolism MH - Neuroinflammatory Diseases MH - *Electroacupuncture MH - *Alzheimer Disease/therapy MH - Hippocampus/metabolism MH - Amyloid beta-Peptides/metabolism OTO - NOTNLM OT - Chinese medicine OT - electroacupuncture OT - fibrin/amyloid-beta deposition OT - high mobility group box protein 1/toll-like receptor 4 OT - receptor for advanced glycation end products/nicotinamide adenine dinucleotide phosphate EDAT- 2023/01/08 06:00 MHDA- 2023/05/01 06:42 CRDT- 2023/01/07 17:04 PHST- 2022/10/26 00:00 [accepted] PHST- 2023/05/01 06:42 [medline] PHST- 2023/01/08 06:00 [pubmed] PHST- 2023/01/07 17:04 [entrez] AID - 10.1007/s11655-023-3592-5 [pii] AID - 10.1007/s11655-023-3592-5 [doi] PST - ppublish SO - Chin J Integr Med. 2023 May;29(5):448-458. doi: 10.1007/s11655-023-3592-5. Epub 2023 Jan 7.