作者
Saravanan S Karuppagounder, Lauren Alin, Yingxin Chen, David Brand, Megan W Bourassa, Kristen Dietrich, Cassandra M Wilkinson, Colby A Nadeau, Amit Kumar, Steve Perry, John T Pinto, Victor Darley‐Usmar, Stephanie Sanchez, Ginger L Milne, Domenico Pratico, Theodore R Holman, S Thomas Carmichael, Giovanni Coppola, Frederick Colbourne, Rajiv R Ratan
发表日期
2018/12
期刊
Annals of neurology
卷号
84
期号
6
页码范围
854-872
简介
Objectives
N‐acetylcysteine (NAC) is a clinically approved thiol‐containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled as an “antioxidant,” poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke.
Methods
Hemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5‐lipoxygenase (ALOX5) knockout mice, and viral‐gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC.
Results
NAC prevented hemin‐induced ferroptosis by neutralizing toxic lipids generated by arachidonate …
学术搜索中的文章
SS Karuppagounder, L Alin, Y Chen, D Brand… - Annals of neurology, 2018