Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.
Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.
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DOI：
10.1371/journal.pone.0120456
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ten VS
中科院分区：
文献类型：
--
作者：
Sosunov SA;Ameer X;Niatsetskaya ZV;Utkina-Sosunova I;Ratner VI;Ten VS
这项研究表明，在遭受缺氧缺血 (HI) 脑损伤的小鼠中，再灌注时启动异氟烷麻醉可通过抑制复合物 I 依赖性线粒体呼吸的恢复来限制线粒体氧化自由基的释放。这显着减轻了氧化应激并减少了 HI 脑损伤的程度。对新生小鼠进行HI，并在再灌注开始时在有或没有机械通气的情况下暴露于异氟烷。在 HI 和异氟醚暴露脑线粒体呼吸结束时，测量 H2O2 排放率，然后评估脑氧化损伤和梗塞体积。 HI 后 8 周评估导航记忆和脑萎缩。在体外，将异氟烷对线粒体 H2O2 排放的直接影响与复合物 I 抑制剂鱼藤酮进行了比较。与对照组相比，15 分钟的异氟醚麻醉抑制了复合物 I 依赖性线粒体呼吸的恢复，并减少了琥珀酸盐支持的线粒体中 H2O2 的产生。与媒介物治疗的 HI 小鼠相比，这与氧化性脑损伤减少、导航记忆增强和脑萎缩减少有关。延长异氟醚麻醉与脑血流 (CBF) 恢复缓慢和神经保护作用丧失有关。然而，当机械通气支持异氟醚麻醉时，CBF 恢复得到改善，与暴露于无呼吸支持的异氟醚的 HI 小鼠相比，该事件与梗塞体积进一步减少相关。因此，在新生小鼠中，再灌注开始时开始的短暂异氟醚麻醉限制了氧化自由基的线粒体释放并减弱了氧化应激。这种新机制有助于异氟烷的神经保护作用。异氟烷麻醉期间使用机械通气可以抵消异氟烷麻醉对脑循环恢复的负面影响，从而增强对再灌注损伤的保护。
This study demonstrates that in mice subjected to hypoxia-ischemia (HI) brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF) and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on recovery of cerebral circulation which potentiates protection against reperfusion injury.
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影响因子：
6.9
作者：
Chen, Hank;Burris, Michael;Fajilan, Adrain;Spagnoli, Fred;Zhang, John H.;Tang, Jiping
通讯作者：
Tang, Jiping
影响因子：
5.7
作者：
Harada, H;Kelly, PJ;Patel, PM
通讯作者：
Patel, PM
影响因子：
4.3
作者：
Agarwal, Bhawana;Dash, Ranjan K.;Stowe, David F.;Bosnjak, Zeljko J.;Camara, Amadou K. S.
通讯作者：
Camara, Amadou K. S.
影响因子：
2.9
作者：
Caspersen, Casper S.;Sosunov, Alexander;Ten, Vadim S.
通讯作者：
Ten, Vadim S.
DOI：
10.1523/jneurosci.6303-11.2012
发表时间：
2012-02-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Niatsetskaya ZV;Sosunov SA;Matsiukevich D;Utkina-Sosunova IV;Ratner VI;Starkov AA;Ten VS
通讯作者：
Ten VS