These authors made equal contributions to this study.
The organotellurium compound ammonium trichloro(dioxoethylene-0,0′) tellurate enhances neuronal survival and improves functional outcome in an ischemic stroke model in mice
Article first published online: 29 MAR 2007
Journal of Neurochemistry
Volume 102, Issue 4, pages 1232–1241, August 2007
How to Cite
Okun, E., Arumugam, T. V., Tang, S.-C., Gleichmann, M., Albeck, M., Sredni, B. and Mattson, M. P. (2007), The organotellurium compound ammonium trichloro(dioxoethylene-0,0′) tellurate enhances neuronal survival and improves functional outcome in an ischemic stroke model in mice. Journal of Neurochemistry, 102: 1232–1241. doi: 10.1111/j.1471-4159.2007.04615.x
- Issue published online: 29 MAR 2007
- Article first published online: 29 MAR 2007
- Received January 5, 2007; revised manuscript received March 16, 2007; accepted March 16, 2007.
Ammonium trichloro(dioxoethylene-0,0′) tellurate (AS101) is a non-toxic organotellurium compound with pleiotropic activities. It was recently shown to induce production of the neurotrophic factor glial cell line-derived neurotrophic factor and to rescue neuronal-like PC-12 cells from neurotrophic factor deprivation-induced apoptosis. In this study, we show that AS101 improves functional outcome and reduces brain damage in a mouse model of focal ischemic stroke. Both pre-stroke and post-stroke intraperitoneal treatments with AS101 reduced infarct size and edema and improved the neurological function of the animals. AS101 treatments reduced both apoptotic and inflammatory caspase activities, and also inhibited protein tyrosine nitration suggesting that AS101 suppresses oxidative stress. Studies of cultured neurons showed that AS101 confers protection against apoptosis induced by either glucose deprivation or the lipid peroxidation product 4-hydroxynonenal. Moreover, AS101 treatment reduced glutamate-induced intracellular calcium elevation, a major contributor to neuronal death in stroke. As AS101 has an excellent safety profile in humans, our pre-clinical data suggest a potential therapeutic benefit of AS101 in patients suffering from stroke and other neurodegenerative conditions.