Competitive Endogenous RNA Network Associated with Pyroptosis in the Acute Phase of Post Traumatic Brain Injury

Abstract Traumatic brain injury (TBI) is a prevalent neurosurgical condition that can lead to significant disability and mortality. This study investigates the role of long non-coding RNAs (lncRNAs) and pyroptosis in neuroinflammation during the acute phase post-TBI. We analyzed 58 pyroptosis-related genes through mRNA-seq in the injured brain of 33 mice subjected to controlled cortical impact (CCI), organized into 11 groups with different time points (0, 1, 2, 3, 4, 6, 12, 24, 72, 148 hours), including a sham control. Notably, due to the significance of 12-hour time point in the acute inflammatory response, it was selected for whole RNA-seq to profile lncRNA expression, which revealed 540 differentially expressed mRNAs (419 upregulated, 121 downregulated) and 95 lncRNAs (42 upregulated, 53 downregulated). Four key pyroptosis genes (Casp4, Il1a, Il1b, and Il6) were significantly overexpressed. Utilizing the R package “multiMiR” and various databases (“miRDB”, “Starbase” and “LncBase v3.0”), we identified miRNA-mRNA and lncRNA-miRNA interactions, culminating in a pyroptosis-associated competitive endogenous RNA (ceRNA) network comprising 4 lncRNAs, 16 miRNAs, and 4 mRNAs. The 4 lncRNAs and 4 mRNAs showed concordance between the targeted gene expression verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and the whole RNA-seq results. Our findings indicate that Casp4-mediated non-canonical pyroptosis may play a critical role during the acute phase following TBI, offering insights into potential therapeutic targets and mechanisms for TBI management.