Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis Mediation
We evaluated the therapeutic effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on behavioral and cognitive function in a mouse model of mild subarachnoid hemorrhage (SAH) and explored the underlying mechanisms in conjunction with the HMGB1–RAGE axis. The SAH models were generated in a to...
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2023-03-01
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author | Harry Jung Dong Hyuk Youn Jeong Jin Park Jin Pyeong Jeon |
author_facet | Harry Jung Dong Hyuk Youn Jeong Jin Park Jin Pyeong Jeon |
author_sort | Harry Jung |
collection | DOAJ |
description | We evaluated the therapeutic effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on behavioral and cognitive function in a mouse model of mild subarachnoid hemorrhage (SAH) and explored the underlying mechanisms in conjunction with the HMGB1–RAGE axis. The SAH models were generated in a total of 126 male C57BL/6J mice via endovascular perforation and evaluated 24 h and 72 h after the intravenous administration of BMSCs (3 × 10<sup>5</sup> cells). The BMSCs were administered once, at 3 h, or twice, at 3 h and 48 h after the model induction. The therapeutic effects of the BMSCs were compared to those of the saline administration. Compared to saline-treated SAH-model mice, at 3 h, the mice with mild SAH treated with the BMSCs showed significant improvements in their neurological scores and cerebral edema. The administration of the BMSCs decreased the mRNA expression of HMGB1, RAGE, TLR4, and MyD88, as well as the protein expression of HMGB1 and phosphorylated NF-kB p65. Furthermore, the numbers of slips per walking time, impairments in short-term memory, and the recognition of novel objects were improved. There was some improvement in inflammatory-marker levels and cognitive function according to the BMSCs’ administration times, but no large differences were seen. The administration of BMSCs improved behavioral and cognitive dysfunction by ameliorating HMGB1–RAGE axis-mediated neuroinflammation after SAH. |
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language | English |
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spelling | doaj.art-89fcb0967da84bca9ca8ff95dcaee3af2023-11-17T20:04:56ZengMDPI AGLife2075-17292023-03-0113488110.3390/life13040881Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis MediationHarry Jung0Dong Hyuk Youn1Jeong Jin Park2Jin Pyeong Jeon3Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of KoreaInstitute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon 24252, Republic of KoreaDepartment of Neurology, Konkuk University Medical Center, Seoul 05030, Republic of KoreaDepartment of Neurosurgery, Hallym University College of Medicine, Chuncheon 24253, Republic of KoreaWe evaluated the therapeutic effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on behavioral and cognitive function in a mouse model of mild subarachnoid hemorrhage (SAH) and explored the underlying mechanisms in conjunction with the HMGB1–RAGE axis. The SAH models were generated in a total of 126 male C57BL/6J mice via endovascular perforation and evaluated 24 h and 72 h after the intravenous administration of BMSCs (3 × 10<sup>5</sup> cells). The BMSCs were administered once, at 3 h, or twice, at 3 h and 48 h after the model induction. The therapeutic effects of the BMSCs were compared to those of the saline administration. Compared to saline-treated SAH-model mice, at 3 h, the mice with mild SAH treated with the BMSCs showed significant improvements in their neurological scores and cerebral edema. The administration of the BMSCs decreased the mRNA expression of HMGB1, RAGE, TLR4, and MyD88, as well as the protein expression of HMGB1 and phosphorylated NF-kB p65. Furthermore, the numbers of slips per walking time, impairments in short-term memory, and the recognition of novel objects were improved. There was some improvement in inflammatory-marker levels and cognitive function according to the BMSCs’ administration times, but no large differences were seen. The administration of BMSCs improved behavioral and cognitive dysfunction by ameliorating HMGB1–RAGE axis-mediated neuroinflammation after SAH.https://www.mdpi.com/2075-1729/13/4/881subarachnoid hemorrhagebone-marrow mesenchymal stem cellscognitive impairmenthigh-mobility group box 1 |
spellingShingle | Harry Jung Dong Hyuk Youn Jeong Jin Park Jin Pyeong Jeon Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis Mediation Life subarachnoid hemorrhage bone-marrow mesenchymal stem cells cognitive impairment high-mobility group box 1 |
title | Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis Mediation |
title_full | Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis Mediation |
title_fullStr | Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis Mediation |
title_full_unstemmed | Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis Mediation |
title_short | Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis Mediation |
title_sort | bone marrow derived mesenchymal stem cells attenuate behavioral and cognitive dysfunction after subarachnoid hemorrhage via hmgb1 rage axis mediation |
topic | subarachnoid hemorrhage bone-marrow mesenchymal stem cells cognitive impairment high-mobility group box 1 |
url | https://www.mdpi.com/2075-1729/13/4/881 |
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