Background: Paroxysmal sympathetic hyperactivity (PSH) is one of the important reasons for the high mortality and morbidity of traumatic brain injury (TBI). We aim to explore the role of the neutrophil extracellular traps (NETs) in the pathogenesis of sympathetic hyperexcitability after TBI and the underlying mechanisms, providing evidence for clinical treatment.Methods: Enzyme-linked immunosorbent assay was used to assess the plasma metanephrine and normetanephrine levels which represented the variation of the sympathetic system after TBI with rat diffuse axonal injury (DAI) model. NETs in the paraventricular nucleus (PVN) and circulating blood were examined using immunofluorescence and flow cytometry. Neutrophils-microglia co-culture system was established to further explore the effect of NETs on PSH and its mechanisms.Results: After TBI, metanephrine and normetanephrine levels began to increase at 9 h and peaked at 72 h. After the injury, the level of NETs kept increasing at 24 and 72 h in the PVN. A positive correlation was found between the concentration of the PVN NETs and blood catecholamine. Flow cytometry of peripheral blood cells revealed that NETs level in the injury group was higher than that in the control group. Immunofluorescence results confirmed the presence of NETs in the PVN after TBI. The positive result of immunoprecipitation suggested a correlation effect between LL37 and P2 × 7. Peptidyl arginine deiminase-4 (PAD4) inhibitor could inhibit the expression levels of MST1, YAP, and IL-1β. The hippo/MST1 pathway inhibitor could inhibit the expression levels of YAP and IL-1β.Conclusion: NETs formation in the PVN might be associated with sympathetic hyperactivity after TBI, which might relate to the activation of microglia cells and increased secretion of IL-1β via the hippo/MST1 pathway.
Messager RNA (mRNA) can be modified in a variety of ways, among which the modification of N6-methyladenosine (m6A) is one of the most common ones. Recent studies have found that the m6A modification in mRNA could functionally regulate the splicing, localization, translation, and stability of mRNA, which might be closely related to multiple diseases. However, the roles of m6A modification in traumatic optic neuropathy (TON) are unknown. Herein, we detected the expression of m6A-related genes via quantitative real-time PCR (qRT-PCR) and performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) as well as RNA-sequencing to analyze the alteration profiles of m6A modification after TON. The results showed that the expression of m6A-related genes (METTL3, WTAP, FTO, and ALKBH5) were all upregulated after TON. In all, 2,810 m6A peaks were differentially upregulated and 689 m6A peaks were downregulated. In addition, the hypermethylated and hypomethylated profiles of mRNA transcripts were also identified. To sum up, our study revealed the differentially expressed m6A modification in the early stage of TON, which may provide novel insights into the mechanism and treatment of TON.
With high morbidity and mortality worldwide, injuries to the central nervous system (CNS) usually result in devastating consequences. However, the underlying mechanisms have not been fully understood and current therapies are still limited.Circular RNA (circRNA) is a novel type of endogenous noncoding RNAs, characterized by covalently closed annular structure. It is gradually recognized that circRNAs are involved in multiple biological processes, such as acting as microRNA sponges or scaffolds during the assembly of protein complex and modulating the transcription of certain genes. Interestingly, circRNAs have been found to be highly expressed in the CNS, which indicates their neurospecificity. Several circRNAs have already been discovered to be associated with multiple pathophysiological processes following neurological diseases. Currently, the molecular roles of circRNAs in CNS injuries have gained increasing attention, leading to uninterrupted relevant researches. Herein, we presented a review of current studies on the role of circRNAs in CNS injuries. The therapeutic potency of circRNAs in CNS injuries was also analyzed. K E Y W O R D S circular RNA, spinal cord injury, stroke, traumatic brain injury S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. Transparent Peer Review Report How to cite this article: Qu X, Li Z, Chen J, Hou L. The emerging roles of circular RNAs in CNS injuries. J Neuro Res.
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