Background Despite therapeutic hypothermia, neonates with hypoxic–ischemic encephalopathy still develop neurological disabilities. We have previously investigated neuroprotection by remote ischemic postconditioning (RIPC) in newborn piglets following hypoxia–ischemia (HI). The aim of this study was to further investigate potential effects of RIPC on cerebral immunohistochemical markers related to edema, apoptosis, and angiogenesis.

Methods Brain expression of aquaporin 4, caspase-3, B-cell lymphoma 2, and vascular endothelial growth factor was analyzed by immunohistochemistry in 23 piglets, randomly selected from a larger study of RIPC after HI. Twenty animals were subjected to 45 minutes of HI and randomized to treatment with and without RIPC, while three animals were randomized to sham procedures. RIPC was conducted by four conditioning cycles of 5-minute ischemia and reperfusion. Piglets were euthanized 72 hours after the HI insult.

Results Piglets subjected to HI treated with and without RIPC were similar at baseline and following the HI insult. However, piglets randomized to HI alone had longer duration of low blood pressure during the insult. We found no differences in the brain expression of the immunohistochemical markers in any regions of interest or the whole brain between the two HI groups.

Conclusion RIPC did not influence brain expression of markers related to edema, apoptosis, or angiogenesis in newborn piglets at 72 hours after HI. These results support previous findings of limited neuroprotective effect by this RIPC protocol. Our results may have been affected by the time of assessment, use of fentanyl as anesthetic, or limitations related to our immunohistochemical methods.

背景尽管进行低温治疗，患有缺氧缺血性脑病的新生儿仍然会出现神经功能障碍。我们之前研究过远程缺血后处理（RIPC）对新生仔猪缺氧缺血（HI）后的神经保护作用。本研究的目的是进一步研究 RIPC 对与水肿、细胞凋亡和血管生成相关的脑免疫组织化学标记物的潜在影响。

方法通过免疫组织化学分析从 HI 后 RIPC 大型研究中随机选择的 23 头仔猪中水通道蛋白 4、caspase-3、B 细胞淋巴瘤 2 和血管内皮生长因子的脑表达。 20 只动物接受 45 分钟的 HI 治疗，并随机接受或不接受 RIPC 治疗，而 3 只动物则随机接受假手术。 RIPC 通过 5 分钟缺血和再灌注的四个调节周期进行。 HI 损伤后 72 小时，仔猪被安乐死。

结果经受 HI 治疗的仔猪在基线和 HI 损伤后的情况相似，无论是否使用 RIPC。然而，随机接受单独 HI 治疗的仔猪在侮辱期间的低血压持续时间较长。我们发现两个 HI 组之间任何感兴趣区域或整个大脑中免疫组织化学标记物的大脑表达没有差异。

结论RIPC 不影响 HI 后 72 小时新生仔猪脑中与水肿、细胞凋亡或血管生成相关的标志物的表达。这些结果支持了该 RIPC 方案神经保护作用有限的先前发现。我们的结果可能受到评估时间、使用芬太尼作为麻醉剂或与我们的免疫组织化学方法相关的限制的影响。