Department of Physiology, The University of Auckland, Auckland, New Zealand.
Pediatr Int. 2020 Jul;62(7):770-778. doi: 10.1111/ped.14215. Epub 2020 Jul 9.
Therapeutic hypothermia is now well established to partially reduce disability in term and near-term infants with moderate-severe hypoxic-ischemic encephalopathy. Preclinical and clinical studies have confirmed that current protocols for therapeutic hypothermia are near optimal. The challenge is now to identify complementary therapies that can further improve outcomes, in combination with therapeutic hypothermia. Overall, anti-excitatory and anti-apoptotic agents have shown variable or even no benefit in combination with hypothermia, suggesting overlapping mechanisms of neuroprotection. Inflammation appears to play a critical role in the pathogenesis of injury in the neonatal brain, and thus, there is potential for drugs with immunomodulatory properties that target inflammation to be used as a therapy in neonates. In this review, we examine the evidence for neuroprotection with immunomodulation after hypoxia-ischemia. For example, stem cell therapy can reduce inflammation, increase cell survival, and promote cell maturation and repair. There are also encouraging preclinical data from small animals suggesting that stem cell therapy can augment hypothermic neuroprotection. However, there is conflicting evidence, and rigorous testing in translational animal models is now needed.
治疗性低温现在已经被证实可以部分减轻中重度缺氧缺血性脑病足月和近足月婴儿的残疾程度。临床前和临床研究已经证实，目前的治疗性低温方案已经接近最佳。现在的挑战是确定与治疗性低温相结合的补充疗法，以进一步改善结果。总的来说，抗兴奋和抗细胞凋亡药物与低温联合使用时表现出不同程度的益处，甚至没有益处，这表明神经保护的机制有重叠。炎症似乎在新生儿脑损伤的发病机制中起关键作用，因此，具有免疫调节特性的药物有可能被用作新生儿的治疗药物。在这篇综述中，我们研究了缺氧缺血后免疫调节的神经保护作用的证据。例如，干细胞疗法可以减少炎症、增加细胞存活并促进细胞成熟和修复。小动物的临床前数据也令人鼓舞，表明干细胞疗法可以增强低温神经保护作用。然而，目前还存在相互矛盾的证据，现在需要在转化动物模型中进行严格的测试。
