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Hydrogen-Rich Saline Regulates Microglial Phagocytosis and Restores Behavioral Deficits Following Hypoxia-Ischemia Injury in Neonatal Mice via the Akt Pathway
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-09-21 , DOI: 10.2147/dddt.s264684 Hongfei Ke 1 , Dexiang Liu 2 , Tingting Li 1 , Xili Chu 1 , Danqing Xin 1 , Min Han 1 , Shuanglian Wang 1 , Zhen Wang 1
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-09-21 , DOI: 10.2147/dddt.s264684 Hongfei Ke 1 , Dexiang Liu 2 , Tingting Li 1 , Xili Chu 1 , Danqing Xin 1 , Min Han 1 , Shuanglian Wang 1 , Zhen Wang 1
Affiliation
Introduction: We have reported previously that hydrogen-rich saline (HS) plays a neuroprotective role in hypoxia-ischemia (HI) brain damage in newborn mice. However, the mechanisms for this neuroprotection resulting from HS remain unknown. In this study, we examined the potential for HS to exert effects upon microglial phagocytosis via involvement of the Akt signaling pathway as one of the neuroprotective mechanisms in response to neonatal HI.
Methods: The HI brain injury model was performed on postnatal day (PND) 7 (modified Vannucci model). The acute brain damage was detected at 3 days after HI exposure. The behavioral and functional screening of the pups at PND11 and PND13 and their long-term outcomes (PND35, 28-days post-HI) were evaluated sensorimotor performance and cognitive functions, respectively.
Results: The result showed that HS administration alleviated HI-induced edema, infract volume and cellular apoptosis within the cortex of neonatal mice. Accompanying these indices of neuroprotection from HS were reductions in HI-induced phagocytosis in microglia as demonstrated in vivo and in vitro, effects that were associated with increasing levels of Akt phosphorylation and improvements in neurobehavioral responses. These beneficial effects of HS were abolished in mice treated with an Akt inhibitor.
Discussion: These results demonstrate that HS treatment attenuates neurobehavioral deficits and apoptosis resulting from HI, effects which were associated with reductions in phagocytosis and appear to involve the Akt signaling pathway.
Keywords: microglia, phagocytosis, hypoxia-ischemia, HS, Akt
中文翻译：
富氢盐水通过 Akt 途径调节小胶质细胞吞噬作用并恢复新生小鼠缺氧缺血损伤后的行为缺陷
简介：我们之前报道过，富氢盐水（HS）在新生小鼠缺氧缺血（HI）脑损伤中发挥神经保护作用。然而，HS 引起的这种神经保护机制仍不清楚。在这项研究中，我们检查了 HS 通过参与 Akt 信号通路对小胶质细胞吞噬作用产生影响的潜力，作为新生儿 HI 的神经保护机制之一。
方法：出生后第7天（PND）建立HI脑损伤模型（改良Vannucci模型）。 HI 暴露后 3 天检测到急性脑损伤。在 PND11 和 PND13 时对幼犬进行行为和功能筛查，并分别评估其长期结果（PND35，HI 后 28 天）的感觉运动表现和认知功能。
结果：结果表明，HS 给药可减轻 HI 引起的新生小鼠皮层水肿、梗塞体积和细胞凋亡。与这些 HS 神经保护指数相伴的是 HI 诱导的小胶质细胞吞噬作用的减少（体内和体外证明），这些作用与 Akt 磷酸化水平的增加和神经行为反应的改善相关。在用 Akt 抑制剂治疗的小鼠中，HS 的这些有益作用被消除了。
讨论：这些结果表明 HS 治疗可减轻 HI 引起的神经行为缺陷和细胞凋亡，这些效应与吞噬作用的减少有关，并且似乎涉及 Akt 信号通路。
关键词:小胶质细胞, 吞噬作用, 缺氧缺血, HS, Akt
更新日期：2020-09-21
Methods: The HI brain injury model was performed on postnatal day (PND) 7 (modified Vannucci model). The acute brain damage was detected at 3 days after HI exposure. The behavioral and functional screening of the pups at PND11 and PND13 and their long-term outcomes (PND35, 28-days post-HI) were evaluated sensorimotor performance and cognitive functions, respectively.
Results: The result showed that HS administration alleviated HI-induced edema, infract volume and cellular apoptosis within the cortex of neonatal mice. Accompanying these indices of neuroprotection from HS were reductions in HI-induced phagocytosis in microglia as demonstrated in vivo and in vitro, effects that were associated with increasing levels of Akt phosphorylation and improvements in neurobehavioral responses. These beneficial effects of HS were abolished in mice treated with an Akt inhibitor.
Discussion: These results demonstrate that HS treatment attenuates neurobehavioral deficits and apoptosis resulting from HI, effects which were associated with reductions in phagocytosis and appear to involve the Akt signaling pathway.
Keywords: microglia, phagocytosis, hypoxia-ischemia, HS, Akt
中文翻译：
富氢盐水通过 Akt 途径调节小胶质细胞吞噬作用并恢复新生小鼠缺氧缺血损伤后的行为缺陷
简介：我们之前报道过，富氢盐水（HS）在新生小鼠缺氧缺血（HI）脑损伤中发挥神经保护作用。然而，HS 引起的这种神经保护机制仍不清楚。在这项研究中，我们检查了 HS 通过参与 Akt 信号通路对小胶质细胞吞噬作用产生影响的潜力，作为新生儿 HI 的神经保护机制之一。
方法：出生后第7天（PND）建立HI脑损伤模型（改良Vannucci模型）。 HI 暴露后 3 天检测到急性脑损伤。在 PND11 和 PND13 时对幼犬进行行为和功能筛查，并分别评估其长期结果（PND35，HI 后 28 天）的感觉运动表现和认知功能。
结果：结果表明，HS 给药可减轻 HI 引起的新生小鼠皮层水肿、梗塞体积和细胞凋亡。与这些 HS 神经保护指数相伴的是 HI 诱导的小胶质细胞吞噬作用的减少（体内和体外证明），这些作用与 Akt 磷酸化水平的增加和神经行为反应的改善相关。在用 Akt 抑制剂治疗的小鼠中，HS 的这些有益作用被消除了。
讨论：这些结果表明 HS 治疗可减轻 HI 引起的神经行为缺陷和细胞凋亡，这些效应与吞噬作用的减少有关，并且似乎涉及 Akt 信号通路。
关键词:小胶质细胞, 吞噬作用, 缺氧缺血, HS, Akt
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