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.