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- Title
Febuxostat attenuates secondary brain injury caused by cerebral hemorrhage through inhibiting inflammatory pathways.
- Authors
Yang Bai; Hongxia Shi; Ying Zhang; Chenyu Zhang; Bin Wu; Xinghan Wu; Zhenwei Fang; Qi Wang; Xiutian Sima; Tiejun Zhang
- Abstract
Objective(s): Neuroinflammation is considered an important step in the progression of secondary brain injury (SBI) induced by cerebral hemorrhage (ICH). The nucleotide-binding and oligomerization structural domain-like receptor family of pyridine structural domain-containing 3 (NLRP3) inflammasomes play an important role in the immune pathophysiology of SBI. Febuxostat (Feb) is a xanthine oxidase inhibitor that is approved for the treatment of gout and has been found to have potent anti-inflammatory effects. However, it has been less studied after ICH and we aimed to explore its protective role in ICH. Materials and Methods: We established an autologous blood-brain hemorrhage model in C57BL/6 mice. Functions of co-expressed genes were analyzed by trend analysis and bioinformatics analysis. Enzyme-linked immunosorbent assay were used to assess the inflammatory factor levels. Fluoro-Jade B histochemistry and TUNEL staining were used to detect neuronal apoptosis. Immunofluorescence staining and western blotting were used to detect the expression of NLRP3 inflammasomes. Results: Pretreatment with Feb reduced neuronal cell death and degeneration and alleviated neurobehavioral disorders in vivo. Feb was found to modulate inflammation-related pathways by trend analysis and bioinformatics analysis. In addition, Feb inhibited microglia activation and elevated cytokine levels after ICH. Furthermore, double immunofluorescence staining showed that co-localization of NLRP3 with Iba1 positive cells was reduced after treatment with Feb. Finally, we found that Feb inhibited the activation of the NLRP3/ASC/caspase-1 pathway after ICH. Conclusion: By inhibiting the NLRP3 inflammasome, preconditioning Feb attenuates inflammatory injury after ICH. Our findings may provide new insights into the role of Feb in neuroprotection.
- Subjects
CEREBRAL hemorrhage; BRAIN injuries; FEBUXOSTAT; NEUROBEHAVIORAL disorders; INTRACEREBRAL hematoma; ENZYME-linked immunosorbent assay
- Publication
Iranian Journal of Basic Medical Sciences, 2024, Vol 27, Issue 6, p740
- ISSN
2008-3866
- Publication type
Article
- DOI
10.22038/IJBMS.2024.74655.16212