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

Brain Behav. 2021 Sep 24;e2354. doi: 10.1002/brb3.2354. Online ahead of print.

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.

Keywords: RNA-sequence analysis of postconditioning; diabetes mellitus; ischemic stroke; neuroprotective effect.