Development of the treatment for neonatal for hypoxia-ischemia (HI) brain injury

炎症反应是缺氧缺血性脑损伤的重要因素。白细胞介素（IL）-18是一种促炎细胞因子，可能是HI后未成熟脑损伤的原因。为探讨HI后低温对发育中脑中IL-18的影响，将7日龄大鼠左侧颈动脉结扎，然后给予8%氧气60 min，并分为低温组（直肠温度32 ℃，持续24 h）和常温组（36 ℃，持续24 h）。与对照组相比，常温组在HI后24 h和72 h同侧大脑半球IL-18 mRNA水平显著升高，而低温组在HI后24 h和72 h同侧大脑半球IL-18 mRNA水平均显著降低。与对照组相比，常温组HI后72 h同侧大脑半球IL-18蛋白水平显著升高，而常温组HI后72 h同侧大脑半球IL-18蛋白水平显著升高，而常温组HI后72 h同侧大脑半球IL-18蛋白水平显著升高。 关于我们 与常温组相比，低温组的血浆中NO水平明显降低。HI后72 h，常温组大鼠大脑皮层、胼胝体和纹状体均可见IL-18阳性细胞，而低温组仅可见少量IL-18阳性细胞。双标记免疫染色发现，大多数IL-18阳性细胞与凝集素共定位，凝集素是小胶质细胞的标志物。与对照组相比，常温组大鼠皮层和CC区的阿米巴样小胶质细胞（AM）数量显著增加，但分支小胶质细胞（RM）数量很少。与常温组相比，低温组皮层和CC中AM数量明显减少，而AM和RM数量与对照组相比无显著性差异。总之，我们发现HI后低温可降低IL-18 mRNA和蛋白水平，HI后低温可降低发育中脑内小胶质细胞的活化。本研究旨在探讨高碳酸血症对新生大鼠缺氧缺血性脑损伤的长期影响。将大鼠单侧颈动脉结扎并暴露于8%氧气中30分钟。在新生大鼠单侧缺氧缺血期间给予6%的二氧化碳，3个月后测定运动功能和神经功能结局。根据Montoya阶梯试验判断，在高碳酸血症动物中观察到显著的运动功能改善。高碳酸血症动物的单侧脑损伤明显改善，这种改善与运动功能表现密切相关。用激光多普勒血流仪监测的缺氧缺血时的脑血流在高碳酸血症动物中保存得更好。我们的研究结果表明，轻度高碳酸血症可能提供持久的运动功能以及神经保护的未成熟的大脑，可能通过增加脑血流量在缺氧缺血。低温是一种潜在的治疗脑缺氧缺血性损伤的不仅是成人，而且是新生儿。然而，低温对发育中的大脑的副作用仍然不清楚，大脑中发生了大量的神经发生。我们研究了神经前体细胞的增殖，全身应用胸苷类似物5-溴脱氧尿苷（BrdU）在新生大鼠在严重的低温环境。将大鼠幼崽分为两组，低温组（30摄氏度）和常温组（37摄氏度）。在各环境中放置21 h后，腹腔注射BrdU标记分裂期细胞，24 h处死。我们检查了脑室周围的脑室下区和齿状回的颗粒下区的BrdU标记细胞的数量。在低温环境中，BrdU标记细胞的数量显着减少，在齿状回，但不是在脑室周围区。因此，严重的低温环境导致新生大鼠神经发生减少。这些观察结果是值得注意的临床低温治疗脑缺氧缺血性损伤在围产期。少

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the prote … More in level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.This study was undertaken to investigate the long-term effect of hypercapnia on neonatal hypoxic-ischemic brain injury, we tested its effect in a neonatal rat hypoxia-ischemia model. The rats were subjected to unilateral carotid artery ligation and exposure to 8% oxygen for 30 minutes. Six percent carbon dioxide was administered to the neonatal rats during unilateral hypoxia-ischemia, and the motor function and neurologic outcomes were determined 3 months later. Significant motor functional improvement was observed in the hypercapnic animals, as judged by the Montoya staircase test. The unilateral brain injury was significantly ameliorated in the hypercapnic animals, and this amelioration was well correlated with the motor functional performance. Cerebral blood flow during hypoxia-ischemia, monitored by laser Doppler flowmetry, was better preserved in the hypercapnic animals. Our results suggest that mild hypercapnia during hypoxia-ischemia may provide long-lasting motor functional as well as neurologic protection for immature brains, possibly by increasing cerebral blood flow during hypoxia.Hypothermia is a potential therapy for cerebral hypoxic ischemic injury of not only adults but also neonates. However, the side effects of hypothermia in the developing brain, where a massive amount of neurogenesis occurs, remain unclear. We investigated the proliferation of neural progenitor cells by systemic application of the thymidine analog 5-bromodeoxyuridine (BrdU) in neonatal rats in a severe hypothermic environment. The rat pups were divided into two groups, a hypothermia group (30 degrees C) and a normothermia group (37 degrees C). After the pups were placed for 21 h in each environment, BrdU was injected intraperitoneally to label dividing cells, and then the pups were sacrificed at 24 h. We examined the number of BrdU-labeled cells in the subventricular zone of the periventricle and the subgranular zone of the dentate gyrus. In the hypothermic environment, BrdU-labeled cells significantly decreased in number in the dentate gyrus, but not in the periventricular region. Thus, the severe hypothermic environment induced a decrease of neurogenesis in the neonatal rat. These observations are noteworthy regarding clinical hypothermia therapy following cerebral hypoxic ischemic injury during the perinatal period. Less