Citation

Zhang D, Lee B, Nutter A, Song P, Dolatabadi N, Parker J, Sanz-Blasco S, Newmeyer T, Ambasudhan R, McKercher SR, Masliah E, Lipton SA. J. Neurochem. 2015; 133(6): 898-908.

Affiliation

Neuroscience and Aging Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, 92037, USA.

Copyright

(Copyright © 2015, John Wiley and Sons)

DOI

10.1111/jnc.13074

PMID

25692407

Abstract

Cyanide is a life threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species (ROS). This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain-barrier to upregulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human induced pluripotent stem cell (hiPSC)-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino (NSA) mouse model of cyanide poisoning that simulates damage observed in the human brain. This article is protected by copyright. All rights reserved.

Language: en