Stewart P A, Magliocco M, Hayakawa K, Farrell C L, Del Maestro R F, Girvin J, Kaufmann J C, Vinters H V, Gilbert J
Microvasc Res. 1987 Mar;33(2):270-82. doi: 10.1016/0026-2862(87)90022-7.
The unique ultrastructure of brain endothelial cells restricts nonspecific leakage of blood-borne molecules across the blood-brain barrier (bbb). Human barrier ultrastructure has not been studied extensively because of the rapid ultrastructural degeneration that takes place after death. We have obtained living, structurally normal neocortex and underlying white matter at biopsy from patients of various ages, and have quantitated ultrastructural features that are associated with the bbb so that we could characterize human barrier ultrastructure and determine whether it changes with age. We found that gray matter capillaries have thinner walls than white matter capillaries, and that during aging white matter capillary walls became thinner until they approached the dimensions of those in gray matter. Thinning is due to loss of pericytes and thinning of the endothelial cytoplasm. The mitochondrial density was found to be higher in gray matter than in white matter, but this is a consequence of there being a smaller cytoplasmic volume and not more (or larger) mitochondria. The mitochondrial population did not change with age. Presumptive nonspecific permeability routes (endothelial vesicles, junctional gaps) did not change with age; therefore we found no morphological substrate for increased nonspecific bbb permeability in the aging human. The loss of pericytes, however, suggests that the bbb in the elderly may be less able to compensate for transient leaks.
脑内皮细胞独特的超微结构限制了血源性分子通过血脑屏障(BBB)的非特异性渗漏。由于死后会迅速发生超微结构退变,人类血脑屏障的超微结构尚未得到广泛研究。我们从不同年龄段的患者活检中获取了结构正常的活体新皮质及其下方的白质,并对与血脑屏障相关的超微结构特征进行了定量分析,以便能够描述人类血脑屏障的超微结构,并确定其是否随年龄变化。我们发现灰质毛细血管壁比白质毛细血管壁薄,并且在衰老过程中,白质毛细血管壁逐渐变薄,直至接近灰质毛细血管壁的尺寸。变薄是由于周细胞丢失和内皮细胞质变薄所致。我们发现灰质中的线粒体密度高于白质,但这是由于细胞质体积较小,而非线粒体数量更多(或更大)的结果。线粒体数量并未随年龄变化。推测的非特异性通透途径(内皮小泡、连接间隙)也未随年龄变化;因此,我们未发现衰老人类血脑屏障非特异性通透性增加的形态学基础。然而,周细胞的丢失表明老年人的血脑屏障可能较难补偿短暂的渗漏。