Yoles E, Zarchin N, Zurovsky Y, Guggenheimer-Furman E, Mayevsky A
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Neurol Res. 1999 Dec;21(8):765-70. doi: 10.1080/01616412.1999.11741011.
Newborns are less sensitive than adults to hypoxic/ischemic injury. However, research into the mechanism of the newborn's relative resistance to reduced brain oxygen levels is relatively scarce, and the time-scale for the disappearance of resistance is not known. The multiprobe assembly (MPA) has enabled us to examine the resistance of puppies at various ages to hypoxia via continuous, simultaneous, on-line measurement of various ionic, metabolic and electrical parameters from the cerebral cortex. The parameters measured included electrocorticogram (ECoG), direct current (DC) steady state potential, extracellular potassium (Ke+) and calcium ion concentrations and intra-mitochondrial Nicotine amide adenine dinucleotide NADH redox levels. These parameters were measured under various degrees of hypoxia (fraction of inspiration oxygen was between 0-10%) in 6-h-old to 24-week-old puppies (n = 44). Sensitivity to hypoxia increased with age, being expressed in the leakage of potassium ions out of the cells (0.3 +/- 0.07 mM in the younger puppies and 3.0 +/- 1.3 mM in the older puppies) following an increase in intra-mitochondrial NADH redox levels. Potassium ion (Ke+) leakage was apparently due to depleted energy stores resulting from an impairment in the balance between oxygen supply and demand. Although the overall effect was similar, the kinetics of these changes were much faster in the older puppies. The time to initial increase of extracellular K+ was 2.5 +/- 0.1 min in the younger puppies and 0.9 +/- 0.1 min in the older puppies. The time to maximum increase of NADH was 3.2 +/- 0.2 min in the younger puppies and 1.4 +/- 0.1 min in the older puppies. Our results indicate that the older puppies utilize the existing oxygen faster than the younger puppies. It is concluded that the increased resistance of newborn puppies to hypoxia is due to intrinsic properties of the brain itself, like the ability of the membrane to maintain ionic homeostasis.
新生儿对缺氧/缺血性损伤的敏感性低于成年人。然而，关于新生儿对脑氧水平降低的相对抵抗力机制的研究相对较少，且抵抗力消失的时间尺度尚不清楚。多探头组件（MPA）使我们能够通过连续、同步、在线测量来自大脑皮层的各种离子、代谢和电参数，来检测不同年龄幼犬对缺氧的抵抗力。所测量的参数包括脑电图（ECoG）、直流（DC）稳态电位、细胞外钾（Ke+）和钙离子浓度以及线粒体内烟酰胺腺嘌呤二核苷酸NADH氧化还原水平。在6小时大至24周大的幼犬（n = 44）中，于不同程度的缺氧（吸入氧分数在0 - 10%之间）情况下测量这些参数。对缺氧的敏感性随年龄增加而增加，表现为线粒体内NADH氧化还原水平升高后，钾离子从细胞中泄漏（年幼幼犬为0.3±0.07 mM，年长幼犬为3.0±1.3 mM）。钾离子（Ke+）泄漏显然是由于氧供需平衡受损导致能量储备耗尽。尽管总体效果相似，但这些变化的动力学在年长幼犬中要快得多。细胞外K+初始升高的时间在年幼幼犬中为2.5±0.1分钟，在年长幼犬中为0.9±0.1分钟。NADH最大升高的时间在年幼幼犬中为3.2±0.2分钟，在年长幼犬中为1.4±0.1分钟。我们的结果表明，年长幼犬比年幼幼犬更快地利用现有氧气。结论是，新生幼犬对缺氧抵抗力的增加是由于大脑自身的内在特性，如膜维持离子稳态的能力。
