2008 Brain Star Award Recipient - Hong-Shuo Sun
Recipient
Hong-Shuo Sun - Biosketch
Post Doctoral Fellow
University of Toronto
Article
Sun HS, Doucette TA, Liu Y, Fang Y, Teves L, Aarts M, Ryan CL, Bernard PB, Lau A, Forder JP, Salter MW, Wang YT, Tasker RA, Tymianski M. Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in the rat. Stroke. 2008 Sep;39(9):2544-53. Epub 2008 Jul 10.
Significance of the paper
Stroke is a leading cause of morbidity and mortality in industrialized countries with the prevalence expected to triple by 2050 and disabilities in afflicted survivors have a significant socioeconomic impact. Whereas few clinical treatments exist for acute stroke, ischemic mechanisms are beginning to be better understood. In this Stroke paper (published July 10, 2008), I extensively extended the previous key discovery of Tymianski lab into in-vivo severe stroke model with hyperthermia and hyperglycemia on the efficacy of NMDAr-PSD95 inhibitors on stroke treatment. In principle, a neuroprotective agent for stroke should address the neurotoxicity of glutamate receptors without causing untoward side-effects, and should be effective when administered after stroke onset in the most adverse model of ischemia (permanent ischemia) even with severe hyperthermia (≥40C) and hyperglycemia.
Here I showed for the first time that neuroprotection in animals subjected to this profound insult of hyperthermia and hyperglycemia is feasible 1hr post-treatment using opeptides that disrupt the interaction of NMDARs with postsynaptic density 95 protein (PSD-95 inhibitors). I used a permanent focal ischemic model (pMCAO) in rats, which causes severe stroke/infarct and hyperthermia. Two PSD95 inhibitors, administrated 1 hr (i.v.) after the pMCAO, reduced infarct size by approximately 50% despite the hyperthermic and non-fasting conditions. PSD95 inhibitors also improved the long-term neurobehavioral functions when treated 3hr (i.v.) after transient stroke. I also used multidisplinary approaches in these projects with telemetry body temperature monitoring system and self-designed / built cooling station for investigating the hyperthermia in stroke. This is translational research and R&D for the NMDA-R/PSD95 inhibitors for treatment of stroke. PSD95 inhibitors have shown high potential to develop into a drug for stroke treatment.