Authors :
Presenting Author: Richard Rasulis, BS – Texas A&M University College of Medicine
Sreevidhya Ramakrishnan, PhD – Texas A&M University College of Medicine
Samba Reddy, PhD, RPh – Texas A&M University Health Science Center
Rationale:
Traumatic brain injury (TBI) is a leading cause of post-traumatic epilepsy (PTE). Recently, we developed a mouse PTE model with robust spontaneous recurrent seizures. This study employs RNA-seq strategy to characterize the transcriptomic profile in the hippocampus and cortex in a PTE model, aiming to delineate gene ontology enrichment patterns and identify differentially expressed genes (DEGs) associated with post-traumatic epileptogenesis.
Methods:
RNA-seq database was generated from hippocampal and cortical tissue collected 7 days post-TBI. Differential gene expression was assessed across 49,315 genes using R-based statistical pipelines. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using open-source databases to elucidate relevant networks and pathways.Results:
There were striking changes in transcriptomic heterogeneity in PTE mice, particularly in transcript abundance across regions, while the types of genes expressed remained largely conserved. KEGG enrichment analysis revealed significant upregulation of pathways involved in synaptic function, neural excitability, and intracellular signal transduction. Region-specific analysis showed minimal overlap in the top ten upregulated and downregulated genes, indicating distinct spatial transcriptional responses to injury. Several DEGs were validated by quantitative PCR. Notably, both pro- and anti-epileptogenic genes were identified and mapped to enriched GO pathways in each brain region.Conclusions:
There are robust, region-specific transcriptomic changes in pathways implicated in epileptogenesis in the PTE model. The presence of distinct gene signatures and enriched pathways may serve as disease-modifying biomarkers to guide therapeutic strategies for PTE.
Funding:
This research was funded by the DOD grant W81XWH2210275.