我们前期研究发现，脑梗死可致远离缺血区的远隔部位甚至周围神经出现继发损害并阻碍神经功能恢复。远隔损害发生机制复杂，兴奋性毒性可能参与其中，但缺乏明确有效的防治手段。新近发现，PSD-95是介导兴奋性毒性的重要物质，脑缺血3小时内应用PSD-95抑制剂在食蟹猴模型中显示出良好的保护作用，但由于严格的时间窗限制，临床可行性差。而远隔损害出现在脑梗死后数天，具备临床可行的干预时间窗，研究PSD-95抑制剂在脑梗死后远隔损害中的作用意义重大。本项目拟采用我们前期研究已成功构建的非人灵长类动物脑梗死模型，术后24小时给予药物或安慰剂，第1、4、12周运用多模态磁共振研究全脑继发性改变模式，同步采用肌电图检测周围神经电生理变化，并联合分子病理学分析上述继发性改变的发生基础，深入探讨PSD-95抑制剂对脑梗死后远隔损害及神经功能的保护作用。研究结果对脑梗死后神经功能恢复将具有重要科学价值和潜在临床意义。

Our previous studies found that cerebral infarction not only led to necrosis in the ischemic core lesion, but also induced secondary damage in nonischemic areas and even peripheral nerves remote from the primary focus, which hampers the neurological function recovery. The underlying mechanisms are complicated, in which excitotoxicity may be involved. Therefore, the targeted prophylactic and therapeutic strategies were limited. Emerging evidence indicates that PSD-95 is the crucial protein mediating excitotoxicity after cerebral infarction, and applying PSD-95 inhibitor within 3 hours following cerebral ischemia have shown promising neuroprotective effect in cynomolgus monkey models. However, due to the restriction of strict time window, the clinical feasibility was limited. The remote lesions occur several days after cerebral infarction and have clinical feasible therapeutic time window. Therefore, investigating the efficacy of PSD-95 inhibitor in remote lesions after cerebral infarction has great significance. To address these issues, the present project is designed to take advantage of an ischemic stroke model of nonhuman primates that we have developed successfully, and to administrate PSD-95 inhibitor or placebo 24 hours following operation. Secondly, multi-modal magnetic resonance imaging is applied to study the secondary change pattern of the whole brain, electromyography to detect the electrophysiological alteration of peripheral nerves and muscles, and molecular pathology to analyze the underlying mechanisms of the secondary changes mentioned above at 1, 4, and 12 week after onset. Finally, we aim to examine the neuroprotective effect of PSD-95 for improving remote lesions and neurological function after cerebral infarction. Findings from the present study would be of great scientific value and potential clinical significance for neurological function recovery following ischemic stroke.