Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct 4;34(14):703-712.
doi: 10.1097/WNR.0000000000001945. Epub 2023 Aug 8.

Febuxostat, a xanthine oxidase inhibitor, regulated long noncoding RNAs and protected the brain after intracerebral hemorrhage

Chenyu Zhang  1   2 , Linqiao Tang  3 , Ying Zhang  1 , Qi Wang  1 , Xueyan Wang  1 , Yang Bai  1 , Zhenwei Fang  1 , Tiejun Zhang  4 , Ting Xu  1   2 , Yuwen Li  1
Affiliations

Febuxostat, a xanthine oxidase inhibitor, regulated long noncoding RNAs and protected the brain after intracerebral hemorrhage

Chenyu Zhang et al. Neuroreport. .

Abstract

Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease and is associated with a high global health burden. Long noncoding RNAs are involved in the pathological damage of ICH. Febuxostat, one of the xanthine oxidase inhibitors, is commonly used in the treatment of hyperuricemia and has been studied in different pathological processes, and its protective effects have been proven in different organs. This study was conducted to investigate whether febuxostat protects brain via regulating long noncoding RNAs after ICH. The modified neurological severity score, wire hanging test, Evans blue perfusion and immunofluorescence were performed to test the protective effects of febuxostat in a mouse model of ICH. Whole transcriptome sequencing was conducted to identify the lncRNAs affected by febuxostat and their functions were analyzed. Febuxostat ameliorated behavioral abnormalities and protected the blood-brain barrier after ICH. Fifteen lncRNAs regulated by febuxostat after ICH were detected. These 15 lncRNAs were associated with 83 gene ontology items. In total, 35 genes, 15 mRNAs and 202 miRNAs were regarded as potential targets for the 15 lncRNAs; 183 co-expressed genes were identified for these 15 lncRNAs and the co-expression network was constructed. Potential binding between lncRNAs and mRNAs was also studied. Enrichment analysis revealed that the functions of the 15 lncRNAs were related to maintaining the blood-brain barrier. This study demonstrated febuxostat protected brain after ICH. Fifteen lncRNAs were regulated and were associated with the effects of febuxostat on BBB integrity after ICH.

PubMed Disclaimer

References

    1. Steiner T, Al-Shahi Salman R, Beer R, Christensen H, Cordonnier C, Csiba L, et al.; European Stroke Organisation. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke 2014; 9:840–855.
    1. Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, et al.; Global Burden of Diseases, Injuries, Risk Factors Study 2010 (GBD 2010). Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health 2013; 1:e259–e281.
    1. Wilkinson DA, Pandey AS, Thompson BG, Keep RF, Hua Y, Xi G. Injury mechanisms in acute intracerebral hemorrhage. Neuropharmacology 2018; 134(Pt B):240–248.
    1. Keep RF, Andjelkovic AV, Xiang J, Stamatovic SM, Antonetti DA, Hua Y, et al. Brain endothelial cell junctions after cerebral hemorrhage: changes, mechanisms and therapeutic targets. J Cereb Blood Flow Metab 2018; 38:1255–1275.
    1. Zhang L, Wang H. Long noncoding RNA in CNS injuries: a new target for therapeutic intervention. Mol Ther Nucleic Acids 2019; 17:754–766.

Publication types

LinkOut - more resources