Early reperfusion is increasingly prioritized in ischemic stroke care, but outcomes remain suboptimal. Therefore, there is an urgent need to find neuroprotective approaches that can be combined with reperfusion to maximize efficacy. Here, the neuroprotective mechanisms behind therapeutic hypothermia were evaluated in a monkey model of ischemic stroke. Focal ischemia was induced in adult rhesus monkeys by placing autologous clots in the middle cerebral artery. Monkeys were treated with tissue plasminogen activator (t-PA) alone or t-PA plus selective intra-arterial cooling (SI-AC). Serial MRI scans and functional deficit were evaluated after ischemia. Histopathology and immunohistochemistry analysis were performed after the final MRI scan. t-PA plus SI-AC treatment led to a higher rate of MRI tissue rescue, and significantly improved neurologic deficits and daily activity scores compared with t-PA alone. In peri-infarct areas, higher fractional anisotropy values and greater fiber numbers were observed in models receiving t-PA plus SI-AC. Histological findings indicated that myelin damage, spheroids, and spongiosis were significantly ameliorated in models receiving SI-AC treatment. White matter integrity was also improved by SI-AC based on immunochemical staining. Our study demonstrates that SI-AC can be effectively combined with t-PA to improve both structural and functional recovery in a monkey model of focal ischemia. These findings provide proof-of-concept that it may be feasible to add neuroprotective agents as adjunctive treatments to reperfusion therapy for stroke.

早期再灌注在缺血性中风治疗中越来越受到重视，但结果仍然不理想。因此，迫切需要找到可以与再灌注相结合的神经保护方法，以最大限度地提高疗效。在这里，在缺血性中风的猴子模型中评估了治疗性低温背后的神经保护机制。通过将自体血块放置在大脑中动脉中，在成年恒河猴中诱导局灶性缺血。猴子单独使用组织纤溶酶原激活剂（t-PA）或t-PA加选择性动脉内冷却（SI-AC）进行治疗。缺血后评估系列 MRI 扫描和功能缺陷。最终 MRI 扫描后进行组织病理学和免疫组织化学分析。与单独使用 t-PA 相比，t-PA 加 SI-AC 治疗可提高 MRI 组织挽救率，并显着改善神经功能缺损和日常活动评分。在梗死周围区域，在接受 t-PA 加 SI-AC 的模型中观察到较高的各向异性分数和较大的纤维数量。组织学结果表明，接受 SI-AC 治疗的模型中髓磷脂损伤、球状体和海绵组织病变均得到显着改善。基于免疫化学染色的 SI-AC 也改善了白质完整性。我们的研究表明，SI-AC 可以有效地与 t-PA 结合，以改善猴局灶性缺血模型的结构和功能恢复。这些发现提供了概念证明，即添加神经保护剂作为中风再灌注治疗的辅助治疗可能是可行的。