The only clinically proven 11treatment for stroke is early reperfusion by thrombolysis or mechanical means. Due to a limited therapeutic window for reperfusion imposed by the rate of stroke progression and the risk of hemorrhagic complications, many patients do not qualify for reperfusion therapy. A potential strategy to increase the therapeutic window for reperfusion is the administration of a neuroprotectant to increase the resiliency of brain tissue during ischemia, slowing the rate of

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... progression and preserving salvageable tissue for delayed reperfusion. PSD-95 inhibitors including Tat-NR2B9c are promising neuroprotectants that interfere with neurotoxic signalling related to NMDA receptor activation after stroke. These compounds have been observed to slow stroke progression in rodent and non-human primate models. Therefore, we tested the hypothesis that Tat-NR2B9c administered 1h into a 4.5h transient middle cerebral artery occlusion(MCAO) in cynomolgus macaques would improve stroke outcomes and reduce stroke volumes 7d following stroke. Twelve cynomolgus macaques underwent MCAO using an aneurysm clip via a trans-Sylvian approach. Six animals received Tat-NR2B9c(2.6mg/kg IV) and 6 received placebo 1 hour following MCAO. The MCA was reperfused 4.5h after MCAO. Animals underwent perfusion MRI immediately after MCAO and diffusion weighted and T2 weighted MRI at 3h, 48h and 7d following MCAO to define stroke volume and perfusion-diffusion mismatch. Animals underwent serial clinical examination post-MCAO using the Non-Human Primate Stroke Scale(NHPSS).Tat-NR2B9c and placebo treated animals had equivalent volumes of tissue at risk by perfusion imaging at baseline. There was a 25% reduction in stroke volume measured by diffusion and T2 MRI(27.16Ϯ1.23mL vs. 20.34Ϯ1.83mL,Pϭ0.011). NHPSS was significantly improved in Tat-NR2B9c treated animals at 7d.(Pϭ0.031)Tat-NR2B9c confers neuroprotection as measured by neurological outcome and stroke volume when administered 1h into a 4.5h MCAO in cynomolgus macaques. This result suggests that early administration of a neuroprotectant can preserve ischemic tissue and improve outcomes with delayed reperfusion. O.02 Rationale, design and preliminary findings of the prospective urban-rural epidemiologic mind (Pure-Mind) MRI Study