Kaya M, Chang L, Truong A, Brightman M W
Laboratory of Neurobiology, NINDS, National Institutes of Health, Bethesda, Maryland 20892-4062, USA.
Exp Neurol. 1996 Nov;142(1):6-13. doi: 10.1006/exnr.1996.0174.
The endothelium responsible for the blood-brain barrier to hydrophilic solutes has been converted here, by chemical means, to the fenestrated, permeable type of vessel (FV). During development, some brain vessels are reported to be transiently fenestrated. Endothelial fenestrae of adrenal glands are known to be reinduced in vitro by retinoic acid (RA) or phorbol myristate acetate (PMA). Could fenestrae be likewise reinduced in brain barrier vessels? When RA or PMA were infused continuously by an osmotic pump for 28 days into the cerebral cortex of rats, some brain vessels in the lesion cavity created by the reagents were FV. There were no FV in adjacent brain. When 100 microM RA was infused, about 20% of vessels in the cyst were FV, as were about 29% after infusion of 150 ng/ml PMA. Fenestra development depended on concentration and time. Reversibility of fenestra formation was complete at 1-2 months after delivery of RA or PMA had ceased. It is proposed that the RA and PMA effect is mediated by the plasminogen activator urokinase, in as much as both RA and PMA stimulate its production. This notion is supported by preliminary experiments in which urokinase infusion into brain also produced fenestrae. It is further suggested that the reversible induction of fenestrae in the mature brain by RA, PMA, and, perhaps, a variety of other conversion factors may be confined to a subset of brain barrier vessels that must be regenerating and of the kind that were temporarily fenestrated during fetal life.
负责对亲水性溶质形成血脑屏障的内皮细胞，在这里已通过化学方法转化为有窗孔的、可渗透型的血管（FV）。在发育过程中，据报道一些脑血管会短暂出现窗孔。已知肾上腺内皮窗孔可在体外被视黄酸（RA）或佛波醇肉豆蔻酸酯乙酸盐（PMA）重新诱导产生。脑血管中的窗孔是否也能被重新诱导产生呢？当通过渗透泵将RA或PMA持续注入大鼠大脑皮层28天时，由这些试剂造成的损伤腔内的一些脑血管为FV。相邻脑组织中则没有FV。当注入100微摩尔的RA时，囊肿内约20%的血管为FV，注入150纳克/毫升PMA后这一比例约为29%。窗孔的形成取决于浓度和时间。在停止给予RA或PMA后1至2个月，窗孔形成的可逆性完全恢复。有人提出，RA和PMA的作用是由纤溶酶原激活剂尿激酶介导的，因为RA和PMA都能刺激其产生。这一观点得到了初步实验的支持，在这些实验中，向脑内注入尿激酶也能产生窗孔。进一步表明，RA、PMA以及可能的多种其他转化因子对成熟脑窗孔的可逆诱导，可能仅限于一部分必须正在再生的脑屏障血管，且这些血管是在胎儿期曾短暂出现窗孔的那种类型。
