Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.

Autor: Xu LL; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Yang S; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Zhou LQ; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Chu YH; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Pang XW; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., You YF; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Zhang H; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Zhang LY; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Zhu LF; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Chen L; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Shang K; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Xiao J; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Wang W; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Tian DS; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. tiands@tjh.tjmu.edu.cn.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China. tiands@tjh.tjmu.edu.cn.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China. tiands@tjh.tjmu.edu.cn.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. tiands@tjh.tjmu.edu.cn., Qin C; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. chuanqin@tjh.tjmu.edu.cn.; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China. chuanqin@tjh.tjmu.edu.cn.; Key Laboratory of Vascular Aging, Tongji Hospital of Tongji Medical College, Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430030, China. chuanqin@tjh.tjmu.edu.cn.; Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. chuanqin@tjh.tjmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2024 Aug 03; Vol. 21 (1), pp. 195. Date of Electronic Publication: 2024 Aug 03.
DOI: 10.1186/s12974-024-03187-4
Abstrakt: Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje