Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus
Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus
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DOI：
10.1152/ajpregu.00404.2006
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发表时间：
2007-03-01
影响因子：
2.8
通讯作者：
Hetherington, Hoby P.
中科院分区：
文献类型：
--
作者：
Douglas, Robert M.;Miyasaka, Naoyuki;Hetherington, Hoby P.
慢性持续性缺氧（CCH）和慢性间歇性缺氧（CIH）对中枢神经系统有有害的影响。由于缺氧暴露模式的不同，病理结果可能会有所不同。n -乙酰天冬氨酸/肌酸（NAA/Cr）比率是神经元完整性的可靠标志，可以通过质子核磁共振波谱法无创测量。P2 CD1小鼠幼崽及其幼崽暴露于CCH，其中FIO2连续保持在11%，或暴露于CIH，其中FIO2每4分钟在21%至11%之间变化。P30小鼠暴露于间歇性缺氧4周后，海马和丘脑的NAA/Cr比值显著降低，随后暴露于正常缺氧4周后，这一现象被逆转。同时，暴露于持续缺氧4周的小鼠在这些大脑区域的NAA/Cr比率与对照组没有任何差异。这些结果表明，间歇性缺氧暴露可能比连续缺氧暴露对神经元功能和完整性有更不利的影响。NAA/Cr水平在正常缺氧恢复过程中逆转至基线水平表明，针对缓解疾病（如阻塞性睡眠呼吸暂停）中间歇性缺氧应激的治疗策略有可能在这些患者中诱导显着的神经认知恢复。
Chronic constant hypoxia (CCH) and chronic intermittent hypoxia (CIH) are known to have deleterious effects on the central nervous system. Because of the difference in the pattern of hypoxic exposure, it is possible that the pathological outcome would vary. The N-acetyl aspartate/creatine (NAA/Cr) ratio is a reliable marker of neuronal integrity, and this can be noninvasively measured by proton nuclear magnetic resonance spectroscopy. P2 CD1 mouse pups with their dams were exposed to either CCH, where the FIO2 was maintained at 11% continuously or to CIH, where the FIO2 was varied between 21 and 11% every 4 min. P30 mice exposed to intermittent hypoxia for 4 wk demonstrated a significant decrease in the NAA/Cr ratio in the hippocampus and thalamus, which was reversed by a subsequent exposure to 4 wk of normoxia. Meanwhile, mice exposed to 4 wk of constant hypoxia did not demonstrate any differences in their NAA/Cr ratios from controls in these brain regions. These results indicate that an intermittent pattern of hypoxic exposure may have a more adverse effect on neuronal function and integrity than a continuous one. The reversal of NAA/Cr levels to baseline during the return to normoxia indicates that therapeutic strategies targeted at alleviating the intermittent hypoxic stress in diseases, such as obstructive sleep apnea, have the potential for inducing significant neurocognitive recovery in these patients.