Raman Lakshmi, Tkac Ivan, Ennis Kathleen, Georgieff Michael K, Gruetter Rolf, Rao Raghavendra
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Brain Res Dev Brain Res. 2005 May 12;156(2):202-9. doi: 10.1016/j.devbrainres.2005.02.013.
The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9-11 microl centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myoinositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios (P < 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia.
在患有青紫型先天性心脏病的儿童中观察到的认知缺陷表明发育中的海马体受到了影响。这些儿童在婴儿期出现的慢性出生后缺氧可能在这些损伤中起作用。为了了解慢性缺氧中海马体损伤的生化机制，使用9.4T的体内1H NMR光谱法，在慢性出生后缺氧的大鼠模型中评估了由海马体中15种代谢物浓度和2种代谢物比率组成的神经化学图谱。通过从出生后第3天（P）到P28连续将大鼠（n = 23）暴露于10%的氧气中来诱导慢性缺氧。在P14、P21和P28时，从以左侧海马体为中心的9 - 11微升体积中对15种代谢物进行定量，并与常氧对照组（n = 14）进行比较。慢性缺氧中神经化学物质的发育轨迹与常氧中观察到的相似。然而，慢性缺氧对以下神经化学物质的浓度有影响：天冬氨酸、肌酸、磷酸肌酸、γ-氨基丁酸（GABA）、谷氨酸、谷氨酰胺、谷胱甘肽、肌醇、N-乙酰天门冬氨酸（NAA）、磷酸乙醇胺以及磷酸肌酸/肌酸（PCr/Cr）和谷氨酸/谷氨酰胺（Glu/Gln）比率（除谷氨酸外，每种P < 0.001，谷氨酸P = 0.04）。PCr/Cr比率升高与脑能量消耗降低一致。鉴于兴奋性神经传递与脑能量代谢之间已确立的联系,我们推测谷氨酸、Glu/Gln比率和GABA升高表明在能量受限环境中兴奋性神经传递受到抑制。NAA和磷酸乙醇胺降低表明神经元完整性和磷脂代谢减少。海马体在发育过程中神经化学的改变可能是人类婴儿慢性缺氧风险中存在的一些认知缺陷的基础。
