EXTRACELLULAR-SPACE PARAMETERS IN THE RAT NEOCORTEX AND SUBCORTICAL WHITE-MATTER DURING POSTNATAL-DEVELOPMENT DETERMINED BY DIFFUSION ANALYSIS
EXTRACELLULAR-SPACE PARAMETERS IN THE RAT NEOCORTEX AND SUBCORTICAL WHITE-MATTER DURING POSTNATAL-DEVELOPMENT DETERMINED BY DIFFUSION ANALYSIS
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DOI：
10.1016/0306-4522(93)90503-8
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发表时间：
1993-07-01
期刊：
影响因子：
3.3
通讯作者：
NICHOLSON, C
中科院分区：
文献类型：
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作者：
LEHMENKUHLER, A;SYKOVA, E;NICHOLSON, C
在出生后的发育过程中，对大鼠躯体感觉新皮层的灰质和皮层下白质测量了脑组织的三个扩散参数：细胞外间隙体积分数、迂曲度和四甲基铵的非特异性摄取。这三个参数是根据出生后2 - 120天体内四甲基铵的浓度 - 时间曲线确定的。四甲基铵浓度是用距离离子电渗源130 - 200微米的离子选择性微电极测量的。利用快速冷冻组织，将数据与0 - 90日龄大鼠的细胞构筑结构和区域平均厚度相关联。细胞外间隙体积分数在新生大鼠中最大，并随年龄增长而减小。在2 - 3日龄的动物中，体积分数（平均值±标准误）在III层和IV层为0.36 ± 0.04，在V层为0.38 ± 0.02，在VI层为0.41 ± 0.01，在白质中为0.46 ± 0.01。体积分数最早在出生后6 - 7天的V层和VI层下降，随后在出生后8 - 9天的III层和IV层以及出生后10 - 11天的白质中下降。在出生后10 - 21天之间，所有皮层和尤其是白质的体积分数进一步大幅下降。在出生后21天到成年（90 - 120天龄）之间，体积分数没有进一步下降。成年的体积分数值为：II层，0.19 ± 0.002；III层，0.20 ± 0.004；IV层，0.21 ± 0.003；V层，0.22 ± 0.003；VI层，0.23 ± 0.007；白质，0.20 ± 0.008。迂曲度的值在1.51 - 1.65之间，非特异性细胞摄取在3.3×10⁻³/秒到6.3×10⁻³/秒之间变化。每个参数的变化在任何年龄都没有统计学意义。这些数据首次描述了发育中的大脑的扩散参数。它们证实了先前组织学所表明的在出生后早期发育过程中相对较大的细胞外体积分数。迂曲度的恒定表明小分子在发育中的大脑中的扩散并不比在成年大脑中更受阻。新生大脑较大的细胞外间隙体积分数相对于成年动物，可显著稀释从细胞释放的离子、代谢物和神经活性物质，并且可能是防止幼小动物缺氧、癫痫发作和扩散性抑制的一个因素。扩散特性也可能在发育过程本身中起重要作用。
Extracellular space volume fraction, tortuosity and nonspecific uptake of tetramethylammonium - three diffusion parameters of brain tissue - were measured in gray matter of the somatosensory neocortex and subcortical white matter of the rat during postnatal development. The three parameters were determined from concentration-time profiles of tetramethylammonium in postnatal days 2-120 in vivo. Tetramethylammonium concentration was measured with ion-selective microelectrodes positioned 130-200 mum from an iontophoretic source. Data were correlated with cytoarchitectonic structure and average thickness of the regions in 0-90-day-old rats using rapidly frozen tissue.Extracellular space volume fraction was largest in the newborn rats and diminished with age. In two- to three-day-old animals, volume fraction (mean +/- S.E.) was 0.36 +/- 0.04 in layers III and IV, 0.38 +/- 0.02 in layer V, 0.41 +/- 0.01 in layer VI and 0.46 +/- 0.01 in white matter. The earliest decrease in volume fraction was found in layers V and VI at postnatal days 6-7 followed by a decrease in layer III and IV at postnatal days 8-9 and in white matter at postnatal days 10-11. A further dramatic reduction in volume fraction occurred in all cortical layers and especially in the white matter between postnatal days 10 and 21. There was no further decrease in volume fraction between postnatal day 21 and adults (90-120 days old). The adult volume fraction values were: layer II, 0.19 +/- 0.002; III, 0.20 +/- 0.004; IV, 0.21 +/- 0.003; V, 0.22 +/- 0.003; VI, 0.23 +/- 0.007; white matter, 0.20 +/- 0.008. Values of tortuosity ranged between 1.51 and 1.65, nonspecific cellular uptake varied from 3.3 x 10(-3)/s to 6.3 x 10(-3)/s. The variations in each parameter were not statistically significant at any age.These data represent the first characterization of diffusion parameters in a developing brain. They confirm previous histological indications of a relatively large extracellular volume fraction during early postnatal development. The constancy of the tortuosity shows that diffusion of small molecules is no more hindered in the developing brain than in the adult. The large extracellular space volume fraction of the neonatal brain could significantly dilute ions, metabolites and neuroactive substances released from cells, relative to release in adults, and may be a factor in preventing anoxia, seizure and spreading depression in young animals. The diffusion characteristics could also play an important role in the developmental process itself.