The neuroprotective effect and RNA‐sequence analysis of postconditioning on the ischemic stroke with diabetes mellitus tree shrew model
| Autor: | Shuqing Li, Xia Li, Qiwei Liao, Shufen Tan, Tingyu Ke, Ling Zhao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Neurosciences. Biological psychiatry. Neuropsychiatry Inflammation Pharmacology Neuroprotection Beta-1 adrenergic receptor Behavioral Neuroscience Diabetes mellitus ischemic stroke medicine Animals RNA‐sequence analysis of postconditioning Original Research Tupaia Sequence Analysis RNA business.industry Tupaiidae medicine.disease neuroprotective effect Histocompatibility Disease Models Animal Neuroprotective Agents Cytokine diabetes mellitus RNA Tumor necrosis factor alpha medicine.symptom Signal transduction business RC321-571 |
| Zdroj: | Brain and Behavior Brain and Behavior, Vol 11, Iss 11, Pp n/a-n/a (2021) |
| ISSN: | 2162-3279 |
| DOI: | 10.1002/brb3.2354 |
| Popis: | Introduction Patients with comorbidity of ischemic stroke (IS) and diabetes mellitus (DM) show poor neurological functional recovery, and ischemic postconditioning (IPOC) should be considered a powerful neuroprotective method for IS. However, whether it should be introduced for patients with IS and DM remains controversial. This study established a DM with IS (DMIS) tree shrew model, which was intervened by IPOC to assess its neuroprotective effects and also to analyze the relevant mechanism by RNA‐sequence and bioinformatics analysis. Methods Fifty‐four tree shrews were randomly divided into a sham operation control group, a DMIS group, and an IPOC group (DMIS model), with 18 tree shrews per group. Triphenyl tetrazolium chloride (TTC), hematoxylin‐eosin (HE) staining, transmission electron microscopy (TEM), and RNA‐sequence analysis were performed to assess the IPOC effect. Results IPOC reduced infarct size and reduced nerve cell injury in IS tree shrews with DM. RNA‐seq analysis showed that IPOC significantly increased the expression of the homeobox protein SIX3, while downregulating the expression of HLA class II histocompatibility antigens DQ beta 1 chain, CAS1 domain‐containing protein 1, and cytokine receptor‐like factor 2. The most downregulated signaling pathways include the NF‐κB signaling pathway, TNF signaling pathway, and Fc gamma R‐mediated phagocytosis. Conclusions IPOCs have a neuroprotective effect in a DMIS animal model that reduces infarct size and nerve cell injury. This mechanism might be related to reducing inflammation and stress responses that decreases the activity of TNF and NF‐κB signaling pathways. IPOC had a neuroprotective effect in a diabetic ischemic stroke model to reduce infarct size and nerve cell damage. Through RNA‐seq analysis, IPOC clearly downregulated the expression of HLA class II histocompatibility antigen DQ beta 1 chain, CAS1 domain‐containing protein 1, and cytokine receptor‐like factor 2. In addition, the downregulation of the NF‐?B signaling pathway, TNF signaling pathway, and Fc gamma R‐mediated phagocytosis indicate these may be the main pathways for IPOC intervention. |
| Databáze: | OpenAIRE |
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