TNFα and microRNA-15b expression changes in experimental model of subarachnoid hemorrhage

Aims: The aim of the present study was to investigate expression changes of pro-inflammatory and pro-apoptototic cytokine TNFα (Tumor Necrosis Factor-alpha) and microRNAs involved its regulation in early pathophysiological changes after SAH. Materials and Methodology: MicroRNA (miR-125b, miR-146a, miR-346, miR-155, miR-15b) and mRNA (TNFα) expression were determined by quantitative real-time PCR in brain tissue samples. A total of 88 animals were divided to Sham, Mild SAH, Severe SAH groups in following time-points: 2h, 4h, 6h, 8h (n=7per group) including 4 animals used as an absolute control. Results: We have found a statistically significant difference in TNFα expression between Sham and Severe SAH groups at all the time-points (p<0,05), between Sham and Mild SAH groups 4 hours after induction of SAH (p<0,05) and between Mild and Severe SAH groups at 2h and 6h time-points (p<0,05). Furthermore, a significant difference in microRNA-15b expression between Sham and Severe SAH groups was observed 8 hours after SAH (p<0,05). All the other miRNAs have not been significantly changed. Conclusions: Subarachnoid hemorrhage was associated with an early increase in TNFα and miR-15b expression especially in Severe SAH groups. Despite of very complex cross-regulation between cytokines and microRNA, information of inflammation/apoptotic mechanism activated within few hours after stroke may improve our knowledge of stroke pathophysiology. Furthermore, it can lead to therapeutic improvement using combination of both pro-apoptotic markers TNFα and miR-15b.