Systematic Analysis of tRNA-Derived Small RNAs Reveals Effects of Xuefu-Zhuyu Decoction on Hippocampus of Rats after Traumatic Brain Injury

2021 ◽  
Author(s):  
Feng Dai ◽  
Tao Tang ◽  
Ruohuang Lu ◽  
Pengfei Li ◽  
Dandan Feng ◽  
...  
Keyword(s):  
Experimental Data ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Rat Model ◽  
Small Rnas ◽  
Target Genes ◽  
Cocaine Addiction ◽  
Therapeutic Effects ◽  
Xuefu Zhuyu Decoction

Abstract Background: Traumatic brain injury (TBI) is one of the most common neurosurgical diseases which refers to brain function impairment or brain pathological changes induced by external causes. A traditional Chinese medicine, Xuefu Zhuyu Decoction (XFZYD), has been indicated to harbor therapeutic property against TBI. Transfer RNA (tRNA)-derived small RNAs i.e., tsRNAs (a group of small RNAs derived from tRNAs) are multifunctional regulatory non-coding RNAs generated under pressure and implicated in the progression of TBI.Methods: TBI model was successfully constructed by using of rats. Further using sequencing and omics to identify novel tsRNAs as drug targets for XFZYD therapy against TBI in rat hippocampus. qPCR assay was used to further verify the experimental results. GO analyzed the signaling pathways of downstream target genes of tsRNA in XFZYD regulated TBI model. qPCR was used to detect the influence of over-expressed tsRNA mimic/inhibitor on their target genes in PC12 cell.Results: Our RNA-Seq data illustrates that 11 tsRNAs were mediated by the XFZYD. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway. We also confirm that Pi4kb, Mlh3, Pcdh9, and Ppp1cb were targets genes of 2 XFZYD regulated tsRNAs in hippocampus of rat model and PC12 cells. Furthermore, biological function analysis revealing potential therapeutic effects of tsRNAs, and results found Mapk1, Gnai1 was the related genes of for XFZYD therapy against TBI.Conclusion: Our work successfully illuminates the efficiency of XFZYD for the treatment of TBI. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway in TBI rat model.

scholarly journals Identification of target genes in neuroinflammation and neurodegeneration after traumatic brain injury in rats

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8324 ◽  
Author(s):  
Jianwei Zhao ◽  
Chen Xu ◽  
Heli Cao ◽  
Lin Zhang ◽  
Xuyang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Target Genes ◽  
Gene Expression Omnibus ◽  
Integrated Analysis ◽  
Positive Regulation ◽  
Chronic Neuroinflammation ◽  
Number Of Patients

Background Traumatic brain injury (TBI) is a common neurological emergency observed in hospitals. A considerable number of patients suffer from long-term disabilities after TBI. This study aimed to identify altered gene expression signatures and mechanisms related to TBI-induced chronic neuroinflammation and neurodegeneration. Methods An integrated analysis was performed using published RNA-sequencing studies to determine TBI-induced differentially expressed genes (DEGs). Based on the DEG data, functional annotation, signal-net, and transcription factor analyses were conducted to understand the mechanism of chronic neuroinflammation and neurodegeneration induced after TBI. Results Two datasets were obtained using the Gene Expression Omnibus database, of which, 6,513 DEGs were identified (6,464 upregulated and 49 downregulated). Positive regulation of biological process, positive regulation of cellular process, nucleus, and heterocyclic compound binding were Gene Ontology terms significantly enriched in post-TBI rat models. Leukocyte transendothelial migration, chemokine signaling pathway, neurotrophin signaling pathway, and longevity-regulating pathway were significantly enriched after TBI. With regard to the signal-net analysis, FOXO3, DGKZ and ILK were considered the most critical genes derived using high–betweenness centrality calculation. A total of 44 TFs, including FOXO1, SRY and KLF4, were predicted to play an important role in the upregulation of gene expression. Using integrated bioinformatics analysis, TBI was found to be associated with a significant inflammatory response and neurodegeneration. FOXO3, apolipoprotein (APOE), microtubule-associated protein tau (MAPT), and TREM2 were probably associated with the TBI pathological process. The mitochondrial electron transport chain may be associated with neurodegeneration in patients with TBI, serving as a potential therapeutic target.

Therapeutic effects of chrysin in a rat model of traumatic brain injury: A behavioral, biochemical, and histological study

Life Sciences ◽  
2019 ◽  
Vol 228 ◽  
pp. 285-294 ◽  
Author(s):  
Masome Rashno ◽  
Alireza Sarkaki ◽  
Yaghoob Farbood ◽  
Mohammad Rashno ◽  
Layasadat Khorsandi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Model ◽  
Histological Study ◽  
Therapeutic Effects
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