Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status
Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status
复制标题
选择性动脉内脑冷却可改善非人类灵长类动物栓塞性中风模型的长期结果：疗效取决于再灌注状态
DOI：
10.1177/0271678x20903697
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发表时间：
2020-03-03
影响因子：
6.3
通讯作者：
Ji, Xunming
中科院分区：
文献类型：
--
作者：
Wu, Di;Chen, Jian;Ji, Xunming
几乎所有的卒中神经保护模式，包括选择性动脉内冷却（SI-AC），都未能从实验室转移到床旁。可能被忽视的原因可能是生物学差距，对再灌注状态的关注不足以及对神经学益处的关注不匹配。为了推进中风翻译，我们描述了一种新的基于血栓的成年恒河猴中风模型。使用组织纤溶酶原激活剂进行动脉内溶栓可导致三种临床相关结局-基于数字减影血管造影的完全、部分和无再通。我们还发现再灌注是SI-AC诱导益处的先决条件，其中具有完全或部分再灌注的模型在急性和慢性阶段均表现出显著减少的梗死体积、减轻的神经功能缺损、改善的上肢运动功能障碍;然而，在没有再灌注的模型中没有观察到进一步的神经保护。总之，我们发现再灌注是SI-AC诱导的神经保护的关键调节剂，并提供了行为和成像水平的长期功能益处的见解。我们的研究结果可能是重要的，不仅为翻译的先决条件和潜在的分子靶点，而且为这个血栓溶栓模型在猴子作为一个强大的工具，进一步翻译中风研究。
Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes – complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.