Altered neurogenic pathways in experimental rat models of ischemic cerebral stroke: A transcriptome based meta-analysis

Abstract

1)ObjectivesPromoting neurogenesis mediated recovery is one of the most sought after strategies in recovery after cerebral stroke. In this paper we elucidate how neurogenesis related genes are altered in the early stroke environment, to hint at potential pathways for therapeutic recovery. Materials and MethodsAround 97 microarray datasets derived from stroke affected rat brains were collected from NCBI-GEO. Datasets were normalized and subjected to meta-analysis in Network Analyst to identify differentially expressed genes. Gene enrichment analyses were carried out using GSEA, and WebGestalt, and results were visualized using Cytoscape Enrichment mapping. ResultsNearly 939 differentially expressing genes were identified in the cerebral stroke group. Among them 30 neurogenesis related genes were identified through enrichment mapping analysis, and 35 genes through Protein- Protein Interaction analysis. Highest upregulated neurogenesis genes were found to be TSPO, GFAP, VIM, and TGFB1. Highest Downregulated neurogenesis genes were found to be THY1, NR1D1, CDK5, STX1B, and NOG. ConclusionsThrough this study, we have identified that during the acute time frame after stroke, majority of the neurogenesis genes related to neural proliferation and neural differentiation are downregulated, while the majority of the genes related to neuronal migration were upregulated. Single or combined therapeutic approach against the identified dysregulated genes could greatly aid neural restoration and functional recovery during the postischemic stage.