Snake venom weakens neurovascular integrity and promotes vulnerability to neuroinflammation.

Autor: Feng Z; Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Xueyuan Ave 1068, Nanshan, Shenzhen 518055, Guangdong, China., Fang C; Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Xueyuan Ave 1068, Nanshan, Shenzhen 518055, Guangdong, China., Yu M; Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Xueyuan Ave 1068, Nanshan, Shenzhen 518055, Guangdong, China., Wang Y; Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Xueyuan Ave 1068, Nanshan, Shenzhen 518055, Guangdong, China; University of Chinese Academy of Sciences, Beijing, China., Abiola OF; Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Xueyuan Ave 1068, Nanshan, Shenzhen 518055, Guangdong, China; University of Chinese Academy of Sciences, Beijing, China., Lin J; Department of Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Liaocheng, Shandong, China., Liu Y; Emergency Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China., Zeng Z; Emergency Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China., Zeng L; Emergency Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China., Mo Z; Emergency Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China. Electronic address: mozhizhun@126.com., Ma Y; Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Xueyuan Ave 1068, Nanshan, Shenzhen 518055, Guangdong, China. Electronic address: yz.ma@siat.ac.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 3), pp. 113586. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1016/j.intimp.2024.113586
Abstrakt: Snake envenomation poses significant medical challenges, particularly in subtropical and tropical regions, with long-term impacts on neurovascular integrity and neuroinflammation remaining underexplored. This study investigates the effects of venom from four species of venomous snakes in southern China-Zhoushan Cobra (Naja atra, NA), Many-banded Krait (Bungarus multicinctus, BM), Five-paced Pit Viper (Deinagkistrodon acutus, DA), and Chinese Moccasin (Protobothrops mucrosquamatus, PM) - on the blood-brain barrier (BBB) and chronic neuroinflammation. Using mass spectrometry, we analyzed venom protein compositions, while cytotoxic effects on mouse brain endothelial cells (bEND.3) were evaluated to determine IC 50 values. In vitro BBB models and in vivo experiments in C57BL/6J mice revealed that NA venom, in particular, significantly compromised BBB integrity without inducing large-scale apoptosis, leading to persistent BBB disruption characterized by increased permeability and selective degradation of extracellular matrix and tight junction proteins. Moreover, to simulate secondary infections that often occur following snakebites, we combined venom exposure with lipopolysaccharide (LPS) treatment, which exacerbated neuroinflammatory responses by intensifying microglial activation and promoting a pro-inflammatory phenotype. These findings highlight the role of snake venom in compromising neurovascular integrity and promoting vulnerability to chronic neuroinflammation, emphasizing the need for further research into venom-induced neuroinflammatory pathways and their potential as therapeutic targets.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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