Arrieta-Cruz Isabel, Pfaff Donald W, Shelley Deborah N
Laboratory of Neurobiology and Behavior, The Rockefeller University, Box 275, 1230 York Avenue, New York, NY 10021, USA.
Exp Neurol. 2007 Jun;205(2):449-60. doi: 10.1016/j.expneurol.2007.03.005. Epub 2007 Mar 12.
Diffuse brain damage following anoxia due to cardiac failure, drowning, carbon monoxide exposure or other accidents constitutes a major medical problem. We have created a novel mouse model using the breathing of pure nitrogen, followed by a recently developed assay that reflects an operational definition of generalized arousal. The operational definition is precise, complete, and leads to quantitative, physical measures in a genetically tractable animal. Exposure to pure nitrogen for controlled periods had a surprising bifurcate effect: about half the mice survived with neurological measures that were virtually normal while the other half died. The new assay detected behavioral deficits unrevealed by neurological screening. Two important features of the results were that (i) deficits were not equal across the circadian cycle, and (ii) deficits were not equal across all the measures within the operational definition of arousal. Specific voluntary motor measurements were decreased in a manner that depended on the phase of the circadian cycle. Sensory responses were also decreased, with an emphasis on vertical movement responses; but, interestingly, fear learning was not damaged. This study establishes the first useful approach to diffuse brain damage in a genetically tractable animal. The model and its outcome measurements will be useful during future attempts at amelioration of acquired neurological disabilities following hypoxic-ischemic injuries.
因心力衰竭、溺水、一氧化碳中毒或其他事故导致缺氧后的弥漫性脑损伤是一个重大的医学问题。我们利用纯氮呼吸创建了一种新型小鼠模型，随后采用了一种最近开发的检测方法，该方法反映了广义觉醒的操作性定义。该操作性定义精确、完整，并能在基因易处理的动物中得出定量的物理测量结果。在可控时间段内暴露于纯氮会产生令人惊讶的分歧效应：约一半的小鼠存活下来，其神经学指标几乎正常，而另一半则死亡。新的检测方法发现了神经学筛查未揭示的行为缺陷。结果的两个重要特征是：（i）昼夜节律周期内的缺陷并不相等，（ii）在觉醒操作性定义中的所有测量指标上的缺陷也不相等。特定的自主运动测量值以依赖于昼夜节律周期阶段的方式降低。感觉反应也降低了，尤其侧重于垂直运动反应；但有趣的是，恐惧学习并未受损。这项研究建立了在基因易处理的动物中研究弥漫性脑损伤的首个有用方法。该模型及其结果测量将有助于未来改善缺氧缺血性损伤后获得性神经功能障碍的尝试。
