University of South Carolina School of Medicine, HSEB, 607 Grove Road, Greenville, SC 29605, United States.
Brain Res Bull. 2013 Sep;98:44-52. doi: 10.1016/j.brainresbull.2013.07.008. Epub 2013 Jul 23.
Resistance to tissue hypoxia is a robust fundamental adaptation to low oxygen supply, and represents a novel neuroscience problem with significance to mammalian physiology as well as human health. With the underlying mechanisms strongly conserved in evolution, the ability to resist tissue hypoxia in natural systems has recently emerged as an interesting model in mammalian physiology research to understand mechanisms that can be manipulated for the clinical management of stroke. The extraordinary ability to resist tissue hypoxia by the naked mole rat (NMR) indicates the presence of a unique mechanism that underlies the remarkable healthy life span and exceptional hypoxia resistance. This opens an interesting line of research into understanding the mechanisms employed by the naked mole rat (Heterocephalus glaber) to protect the brain during hypoxia. In a series of studies, we first examined the presence of neuroprotection in the brain cells of naked mole rats (NMRs) subjected to hypoxic insults, and then characterized the expression of such neuroprotection in a wide range of time intervals. We used oxygen nutrient deprivation (OND), an in vitro model of resistance to tissue hypoxia to determine whether there is evidence of neuronal survival in the hippocampal (CA1) slices of NMRs that are subjected to chronic hypoxia. Hippocampus neurons of NMRs that were kept in hypoxic condition consistently tolerated OND right from the onset time of 5h. This tolerance was maintained for 24h. This finding indicates that there is evidence of resistance to tissue hypoxia by CA1 neurons of NMRs. We further examined the effect of hypoxia on metabolic rate in the NMR. Repeated measurement of metabolic rates during exposure of naked mole rats to hypoxia over a constant ambient temperature indicates that hypoxia significantly decreased metabolic rates in the NMR, suggesting that the observed decline in metabolic rate during hypoxia may contribute to the adaptive mechanism used by the NMR to resist tissue hypoxia. This work is aimed to contribute to the understanding of mechanisms of resistance to tissue hypoxia in the NMR as an important life-sustaining process, which can be translated into therapeutic interventions during stroke.
抵抗组织缺氧是一种对低氧供应的强大基本适应，代表了一个新的神经科学问题，对哺乳动物生理学以及人类健康具有重要意义。由于潜在机制在进化中得到了强烈的保守，因此在自然系统中抵抗组织缺氧的能力最近成为了哺乳动物生理学研究中的一个有趣模型，用于理解可以为中风的临床管理而操纵的机制。裸鼹鼠（NMR）抵抗组织缺氧的非凡能力表明存在一种独特的机制，这种机制是其拥有惊人的健康寿命和出色的缺氧抗性的基础。这为研究了解裸鼹鼠（ Heterocephalus glaber ）在缺氧期间保护大脑所采用的机制开辟了一个有趣的研究方向。在一系列研究中，我们首先研究了缺氧应激下裸鼹鼠（NMR）脑细胞中是否存在神经保护作用，然后在广泛的时间间隔内对其进行了特征描述。我们使用氧营养剥夺（OND），这是一种抵抗组织缺氧的体外模型，以确定在慢性缺氧下的 NMR 海马（CA1）切片中是否存在神经元存活的证据。处于缺氧状态下的 NMR 海马神经元从 OND 的起始时间 5 小时开始一直耐受 OND。这种耐受性可维持 24 小时。这一发现表明，NMR 的 CA1 神经元具有抵抗组织缺氧的证据。我们进一步研究了缺氧对 NMR 代谢率的影响。在恒定环境温度下，裸鼹鼠暴露于缺氧期间多次测量代谢率的结果表明，缺氧显著降低了 NMR 的代谢率，这表明缺氧期间代谢率的下降可能有助于 NMR 抵抗组织缺氧的适应机制。这项工作旨在促进对 NMR 抵抗组织缺氧机制的理解，这是一个重要的维持生命的过程，该过程可以转化为中风期间的治疗干预。
