Key result
DY-9760e significantly reduced brain infarct size in a rat model of microsphere embolism-induced cerebral ischemia, associated with complete inhibition of NO production and protein tyrosine nitration.
Why the study?
Does DY-9760e reduce brain infarct size and inhibit NO production in a rat microsphere embolism model?
Does DY-9760e reduce brain infarct size and inhibit NO production in a rat microsphere embolism model?
DY-9760e provides neuroprotection in a rat model of microsphere embolism by inhibiting nitric oxide production and protein tyrosine nitration.
Supports neuroprotection via NO inhibition in rat embolism; leaves open translation to human stroke trials.
Microsphere embolism (ME)-induced ischemia model in rat resembles to multiple brain embolism in human with several clinical features. We here tested whether nitric oxide (NO) production contributes to the neuronal injury in the ME model. A novel calmodulin antagonist, DY-9760e, having a potent inhibitory effect on neuronal nitric oxide synthase (nNOS), reduced brain infarct size in the ME-induced brain ischemia. Consistent with our previous observation with gerbil ischemia/reperfusion model, DY-9760e completely inhibited NO production immediately after and 24 or 48 h after ME. Unlike the gerbil ischemia/reperfusion model, protein tyrosine nitration markedly increased 6-48 h after ME. DY-9760e treatment completely inhibited the marked increase in the protein tyrosine nitration at 24 h after ME. These results suggest that the inhibition of NO production and protein tyrosine nitration by DY-9760e contribute to its neuroprotective action in the ME-induced brain damage.
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Shirakura et al. (2005) studied Microsphere embolism (ME)-induced cerebral ischemia. DY-9760e vs. Vehicle (5% glucose) was evaluated on Infarct area at 72 hours after microsphere embolism (p=<0.05). DY-9760e significantly reduced brain infarct size in a rat model of microsphere embolism-induced cerebral ischemia, associated with complete inhibition of NO production and protein tyrosine nitration.
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