Non-additive effects of delayed connexin hemichannel blockade and hypothermia after cerebral ischemia in near-term fetal sheep
Non-additive effects of delayed connexin hemichannel blockade and hypothermia after cerebral ischemia in near-term fetal sheep
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DOI：
10.1038/jcbfm.2015.171
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发表时间：
2015-12-01
影响因子：
6.3
通讯作者：
Gunn, Alistair J.
中科院分区：
文献类型：
--
作者：
Davidson, Joanne O.;Rout, Alexandra L.;Gunn, Alistair J.
低温对新生儿缺氧缺血性脑病具有部分神经保护作用。封闭连接蛋白半通道可促进缺血后近足月胎羊脑活动的恢复和细胞存活。在这项研究中，我们研究了延迟低温与连接蛋白半通道阻断结合脑室内输注模拟肽是否可以进一步改善脑缺血后的结果。胎羊（妊娠0.85）接受30分钟的脑缺血，然后在开始给药前进行3小时的恢复期。将胎仔随机分配至以下治疗组之一：常温（n = 8）、低温3天（n = 8）、连接蛋白半通道阻断（50 μ mol/L脑室内1小时，随后50 μ mol/L脑室内24小时，n = 8）或低温+半通道阻断（n = 7）。恢复7天后，低温与癫痫发作负担减轻、脑电图（EEG）功率改善、神经元和少突胶质细胞存活率显著增加以及Iba 1阳性小胶质细胞诱导减少相关。相反，尽管半通道阻滞可降低癫痫发作负荷，但对EEG功率或组织学无影响（P < 0.05）。联合低温加半通道阻滞的结局没有进一步改善。总之，这些数据表明，在近期胎羊脑缺血后，联合低温和半通道阻滞没有额外的神经保护作用。
Hypothermia is partially neuroprotective after neonatal hypoxic-ischemic encephalopathy. Blockade of connexin hemichannels can improve recovery of brain activity and cell survival after ischemia in near-term fetal sheep. In this study, we investigated whether combining delayed hypothermia with connexin hemichannel blockade with intracerebroventricular infusion of a mimetic peptide can further improve outcomes after cerebral ischemia. Fetal sheep (0.85 gestation) received 30 minutes of cerebral ischemia followed by a 3-hour recovery period before treatment was started. Fetuses were randomized to one of the following treatment groups: normothermia (n = 8), hypothermia for 3 days (n = 8), connexin hemichannel blockade (50 mu mol/L intracerebroventricular over 1 hour followed by 50 mu mol/L over 24 hours, n = 8) or hypothermia plus hemichannel blockade (n = 7). After 7 days recovery, hypothermia was associated with reduced seizure burden, improved electroencephalographic (EEG) power, and a significant increase in neuronal and oligodendrocyte survival and reduced induction of Iba1-positive microglia. In contrast, although hemichannel blockade reduced seizure burden, there was no effect on EEG power or histology (P < 0.05). There was no further improvement in outcomes with combined hypothermia plus hemichannel blockade. In conclusion, these data show that there is no additive neuroprotection with combined hypothermia and hemichannel blockade after cerebral ischemia in near-term fetal sheep.