Argon reduces neurohistopathological damage and preserves functional recovery after cardiac arrest in rats

Argon reduces neurohistopathological damage and preserves functional recovery after cardiac arrest in rats
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DOI:
10.1093/bja/aes509
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发表时间:
2013-06-01
影响因子:
9.8
通讯作者:
Fries, M.
Fries, M.
中科院分区:
医学1区
文献类型:
--
作者:
Bruecken, A.;Cizen, A.;Fries, M.

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氙在神经损伤后具有深刻的神经保护作用,目前正在心脏骤停患者中进行2期临床试验。然而,氙是非常昂贵的,这可能妨碍其广泛使用。我们假设氩,这是更容易,也可能保护中枢神经组织,并允许更好的功能恢复在啮齿动物模型的全脑ischaemia.14雄性SpragueDawley大鼠进行7分钟的心脏骤停和3分钟的心肺复苏(CPR)。成功CPR后1小时,动物被随机分配至70氩气/氧气(n 7)通气1小时或70氮气(对照组,n 7)。在随后的7天内,每天计算神经功能缺损评分(NDS),然后处死动物,收获脑组织进行组织病理学分析。对照组大鼠有严重的神经功能障碍,而氩气治疗的动物在所有时间点的NDS显着改善。我们的研究表明,一个单一的1h应用70氩显着减少组织病理学损伤的新皮层和海马CA 3/4区域的神经元损伤指数显着减少,与功能性神经恢复的显着改善。
Xenon has profound neuroprotective effects after neurological injury and is currently undergoing phase 2 clinical trials in cardiac arrest patients. However, xenon is very costly, which might preclude its widespread use. We hypothesized argon, which is more available, might also protect central nervous tissues and allow better functional recovery in a rodent model of global cerebral ischaemia.Fourteen male SpragueDawley rats were subjected to 7 min of cardiac arrest and 3 min of cardiopulmonary resuscitation (CPR). One hour after successful CPR, animals were randomized to either ventilation with 70 argon in oxygen (n 7) for 1 h or 70 nitrogen (controls, n7). A neurological deficit score (NDS) was calculated daily for the following 7 days, then the animals were killed and the brains harvested for histopathological analyses.All animals survived. Control rats had severe neurological dysfunction, while argon-treated animals showed significant improvements in the NDS at all time points. This was paralleled by a significant reduction in the neuronal damage index in the neocortex and the hippocampal CA 3/4 region.Our study demonstrates that a single 1 h application of 70 argon significantly reduced histopathological damage of the neocortex and hippocampus, associated with a marked improvement in functional neurological recovery.