TY  - JOUR
PY  - 2015//
TI  - Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid
JO  - Journal of neurochemistry
A1  - Zhang, Dongxian
A1  - Lee, Brian
A1  - Nutter, Anthony
A1  - Song, Paul
A1  - Dolatabadi, Nima
A1  - Parker, James
A1  - Sanz-Blasco, Sara
A1  - Newmeyer, Traci
A1  - Ambasudhan, Rajesh
A1  - McKercher, Scott R.
A1  - Masliah, Eliezer
A1  - Lipton, Stuart A.
SP  - 898
EP  - 908
VL  - 133
IS  - 6
N2  - 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.<p /> <p>Language: en</p>
LA  - en
SN  - 0022-3042
UR  - http://dx.doi.org/10.1111/jnc.13074
ID  - ref1
ER  -