Evaluating the comorbidities of age and cigarette smoking on stroke outcomes in the context of anti-complement mitigation strategies.
Evaluating the comorbidities of age and cigarette smoking on stroke outcomes in the context of anti-complement mitigation strategies.
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DOI：
10.3389/fimmu.2023.1161051
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发表时间：
2023
影响因子：
7.3
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中科院分区：
文献类型：
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多种神经保护剂已经在中风的啮齿动物模型中显示出有益的效果，但它们在临床上未能转化。从这个角度来看，我们认为这一失败的一个可能的解释，至少在一定程度上是因为在临床前卒中模型中对功能结果的评估不足，以及使用不具有临床队列代表性的年轻健康动物。尽管老年和吸烟并存对中风预后的影响在临床上已经有了很好的记录，但这些(和其他)中风并存对中风后神经炎性反应的影响以及对神经保护剂的反应在很大程度上仍未被探索。我们已经证明，一种针对缺血半暗带并抑制补体激活的补体抑制剂(B4Crry)，可以减少神经炎症，改善小鼠缺血性中风后的预后。从这个角度来看，我们讨论了年龄和吸烟并存对卒中后预后的影响，并从实验上评估了补体激活增加是否导致这些并存的急性预后恶化。我们发现，衰老和吸烟的促炎作用会导致更糟糕的中风结果，而这些影响可以通过抑制补体来缓解。
Multiple neuroprotective agents have shown beneficial effects in rodent models of stroke, but they have failed to translate in the clinic. In this perspective, we consider that a likely explanation for this failure, at least in part, is that there has been inadequate assessment of functional outcomes in preclinical stroke models, as well the use of young healthy animals that are not representative of clinical cohorts. Although the impact of older age and cigarette smoking comorbidities on stroke outcomes is well documented clinically, the impact of these (and other) stroke comorbidities on the neuroinflammatory response after stroke, as well as the response to neuroprotective agents, remains largely unexplored. We have shown that a complement inhibitor (B4Crry), that targets specifically to the ischemic penumbra and inhibits complement activation, reduces neuroinflammation and improves outcomes following murine ischemic stroke. For this perspective, we discuss the impact of age and smoking comorbidities on outcomes after stroke, and we experimentally assess whether increased complement activation contributes to worsened acute outcomes with these comorbidities. We found that the pro-inflammatory effects of aging and smoking contribute to worse stroke outcomes, and these effects are mitigated by complement inhibition.