Intramyocardial Injection of Human Adipose-Derived Stem Cells Ameliorates Cognitive Deficit By Regulating Oxidative Stress-Mediated Hippocampal Damage After Myocardial Infarction
| Autor: | Horng-Jyh Harn, Po-Cheng Lin, Cheng-Che Lee, Chuang Ming-Hsi, Tsung-Ming Lee, Tzyy-Wen Chiou, Shinn Zong Lin, Chun-Hung Chen, Chuang Chi-Hsuan |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Myocardial Infarction Adipose tissue Hippocampus Hippocampal formation Pharmacology medicine.disease_cause Superoxides Drug Discovery Medicine Animals Humans Cognitive Dysfunction Passive avoidance test Rats Wistar Human adipose-derived stem cells Genetics (clinical) Cognitive deficit business.industry Myocardium Stem Cells Brain Transplantation Oxidative Stress Adipose Tissue Synaptic plasticity Molecular Medicine Original Article Cognitive function Stem cell medicine.symptom business Reactive oxygen species beta 2-Microglobulin Oxidative stress Stem Cell Transplantation |
| Zdroj: | Journal of Molecular Medicine (Berlin, Germany) |
| DOI: | 10.21203/rs.3.rs-648732/v1 |
| Popis: | Cognitive impairment is a serious side effect of post-myocardial infarction (MI) course. We have recently demonstrated that human adipose-derived stem cells (hADSCs) ameliorated myocardial injury after MI by attenuating reactive oxygen species (ROS) levels. Here, we studied whether the beneficial effects of intramyocardial hADSC transplantation can extend to the brain and how they may attenuate cognitive dysfunction via modulating ROS after MI. After coronary ligation, male Wistar rats were randomized via an intramyocardial route to receive either vehicle, hADSC transplantation (1 × 106cells), or the combination of hADSCs and 3-Morpholinosydnonimine (SIN-1, a peroxynitrite donor). Whether hADSCs migrated into the hippocampus was assessed by using human-specific primers in qPCR reactions. Passive avoidance test was used to assess cognitive performance. Postinfarction was associated with increased oxidative stress in the myocardium, circulation, and hippocampus. This was coupled with decreased numbers of dendritic spines as well as a significant downregulation of synaptic plasticity consisting of synaptophysin and PSD95. Step-through latency during passive avoidance test was impaired in vehicle-treated rats after MI. Intramyocardial hADSC injection exerted therapeutic benefits in improving cardiac function and cognitive impairment. None of hADSCs was detected in rat’s hippocampus at the 3rd day after intramyocardial injection. The beneficial effects of hADSCs on MI-induced histological and cognitive changes were abolished after adding SIN-1. MI-induced ROS attacked the hippocampus to induce neurodegeneration, resulting in cognitive deficit. The remotely intramyocardial administration of hADSCs has the capacity of improved synaptic neuroplasticity in the hippocampus mediated by ROS, not the cell engraftment, after MI.Key messagesHuman adipose-derived stem cells (hADSCs) ameliorated injury after myocardial infarction by attenuating reactive oxygen species (ROS) levels.Intramyocardial administration of hADSCs remotely exerted therapeutic benefits in improving cognitive impairment after myocardial infarction.The improved synaptic neuroplasticity in the hippocampus was mediated by hADSC-inhibiting ROS, not by the stem cell engraftment. |
| Databáze: | OpenAIRE |
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