The neuroprotective effect and RNA‐sequence analysis of postconditioning on the ischemic stroke with diabetes mellitus tree shrew model

Abstract

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.

Tree shrews as a new animal model for systemic sclerosis research

“…Furthermore, tree shrews possess several advantageous traits, including their small size, short reproductive cycle and lifespan, and low feeding costs, thereby combining the benefits of both primates and rodents (18). Notably, tree shrews have been extensively employed in the establishment of disease models for viral hepatitis, neuropsychiatric disorders, metabolic ailments, visual impairments, and cancers, thereby showcasing unique advantages that have garnered recognition across various medical disciplines (19)(20)(21)(22)(23). In recent years, researchers have increasingly turned to tree shrews as a valuable resource for constructing animal models of autoimmune diseases, successfully establishing models for rheumatoid arthritis and systemic lupus erythematosus in tree shrews (24,25).…”

“…To gain a deeper understanding of genes and their involvement in various biological processes, gene sequencing and bioinformatics methods have become indispensable tools in molecular biology and genetics research (27-29). Recently, the application of RNA sequencing has facilitated the investigation of the transcriptional profile of brain tissue in the tree shrew model of diabetes complicated with ischemic stroke (22), as well as the transcriptional landscape of the liver in the tree shrew model of diabetic liver disease (30). However, no relevant study has explored the transcriptome sequencing of tree shrew skin.…”