PMID- 37738917 OWN - NLM STAT- Publisher LR - 20231022 IS - 1532-8511 (Electronic) IS - 1052-3057 (Linking) VI - 32 IP - 11 DP - 2023 Nov TI - Bone marrow mesenchymal stem cells-derived exosomes mediated delivery of tetramethylpyrazine attenuate cerebral ischemic injury. PG - 107369 LID - S1052-3057(23)00392-0 [pii] LID - 10.1016/j.jstrokecerebrovasdis.2023.107369 [doi] AB - OBJECTIVES: Tetramethylpyrazine (TEP) can protect the brain from ischemic damage, but it has defects such as short half-life, fast absorption, wide distribution, and rapid elimination, which limits its application. Exosomes (Exos) have the property of loading drugs and transporting signal substances. Here, we elucidated the effect of TEP-loaded bone marrow mesenchymal stem cell (BMSC)-derived Exos (Exo-TEP) on cerebral ischemic injury. MATERIALS AND METHODS: The Exos were extracted by ultracentrifugation and TEP was loaded into the Exos by electroporation. Oxygen-glucose deprivation (OGD) induced-primary cortical neurons and middle cerebral artery occlusion (MCAO)-induced mouse models were used to determine the effect of Exo-TEP on cerebral ischemic injury in vitro and in vivo. RESULTS: Exo-TEP exhibited a stable and sustained release pattern compared to free TEP. Exo-TEP treatment was more significant in improving OGD-mediated decrease in cell activity, as well as a elevation in apoptosis and ROS production in cortical neurons. In comparison with Exo and free TEP treatment, Exo-TEP treatment significantly improved pathological changes, shrunk cerebral infarction volume, as well reduced neurological deficit scores and neuronal apoptosis, and oxidative stress. CONCLUSIONS: Exo-TEP was superior to free TEP in improving cerebral ischemic injury by reducing neuronal apoptosis and oxidative stress. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Zhang, Guozhen AU - Zhang G AD - Neurosurgery Department, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, 100700, China. Electronic address: guozhen9119@163.com. FAU - Xu, Bin AU - Xu B AD - Neurosurgery Department, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, 100700, China. FAU - Mao, Jinlong AU - Mao J AD - Neurosurgery Department, the Chinese PLA General Hospital 7th Medical Center, Beijing, 100000, China. FAU - Liu, Ruicun AU - Liu R AD - Neurosurgery Department, Tsinghua University Yuquan Hospital, Beijing, 100000, China. LA - eng PT - Journal Article DEP - 20230920 PL - United States TA - J Stroke Cerebrovasc Dis JT - Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association JID - 9111633 SB - IM OTO - NOTNLM OT - Apoptosis OT - Bone marrow mesenchymal stem cells OT - Cerebral ischemic OT - Exosomes OT - Tetramethylpyrazine COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2023/09/23 11:42 MHDA- 2023/09/23 11:42 CRDT- 2023/09/22 18:10 PHST- 2023/07/30 00:00 [received] PHST- 2023/08/21 00:00 [revised] PHST- 2023/09/12 00:00 [accepted] PHST- 2023/09/23 11:42 [pubmed] PHST- 2023/09/23 11:42 [medline] PHST- 2023/09/22 18:10 [entrez] AID - S1052-3057(23)00392-0 [pii] AID - 10.1016/j.jstrokecerebrovasdis.2023.107369 [doi] PST - ppublish SO - J Stroke Cerebrovasc Dis. 2023 Nov;32(11):107369. doi: 10.1016/j.jstrokecerebrovasdis.2023.107369. Epub 2023 Sep 20.