Lehmenkühler A, Syková E, Svoboda J, Zilles K, Nicholson C
Institute of Physiology, University of Münster, Germany.
Neuroscience. 1993 Jul;55(2):339-51. doi: 10.1016/0306-4522(93)90503-8.
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 microns 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.
在出生后发育过程中，对大鼠体感新皮层灰质和皮层下白质中细胞外间隙体积分数、曲折度和四甲基铵的非特异性摄取（脑组织的三个扩散参数）进行了测量。这三个参数是根据出生后第2至120天体内四甲基铵的浓度-时间曲线确定的。使用离子选择性微电极测量距离子电泳源130 - 200微米处的四甲基铵浓度。利用快速冷冻组织，将数据与0 - 90日龄大鼠各区域的细胞结构和平均厚度相关联。细胞外间隙体积分数在新生大鼠中最大，并随年龄减小。在出生后2至3天的动物中，III层和IV层的体积分数（平均值±标准误）为0.36±0.04，V层为0.38±0.02，VI层为0.41±0.01，白质为0.46±0.01。最早的体积分数下降在出生后第6 - 7天出现在V层和VI层，随后在出生后第8 - 9天出现在III层和IV层，在出生后第10 - 11天出现在白质。在出生后第10至21天，所有皮层层尤其是白质中的体积分数进一步急剧下降。在出生后第21天至成年（90 - 120日龄）之间，体积分数没有进一步下降。成年时的体积分数值为：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。曲折度值在1.51至1.65之间，非特异性细胞摄取从3.3×10⁻³/s变化到6.3×10⁻³/s。每个参数在任何年龄的变化在统计学上均无显著意义。这些数据首次描述了发育中大脑的扩散参数。它们证实了先前组织学上关于出生后早期发育期间细胞外体积分数相对较大的迹象。曲折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人大脑中受到更多阻碍。相对于成体释放而言，新生大脑较大的细胞外间隙体积分数可显著稀释细胞释放的离子、代谢物和神经活性物质，并且可能是预防幼小动物缺氧、癫痫发作和扩散性抑制的一个因素。扩散特性在发育过程本身中也可能起重要作用。
