Sharma H S, Westman J, Navarro J C, Dey P K, Nyberg F
Institute of Neuropathology, Free University Berlin, Germany.
Behav Brain Res. 1995 Dec 14;72(1-2):189-96. doi: 10.1016/0166-4328(96)00170-2.
The possibility that endogenous serotonin (5-hydroxytryptamine, 5-HT) participates in alteration of the blood-brain barrier (BBB) following short-term forced swimming (FS) exercise was examined in a rat model. Subjection of conscious young (age 8-9 weeks, 80-90 g) animals to continuous FS (at a water temperature of 30 +/- 1 degrees C) for 30 min, increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in six and nine brain regions, respectively. The EBA staining was noted in posterior cingulate cortex, parietal, occipital cortices, cerebellar vermis, medial lateral cerebellar cortices and dorsal surface of hippocampus. In addition to these brain regions, the BBB permeability to 131I-sodium was further extended to caudate nucleus, thalamus and hypothalamus. This effect of FS on the BBB permeability was absent in adult (age 24-30 weeks, 300-400 g) animals. Measurement of 5-HT showed a profound increase of plasma and brain in young rats by 180% and 250%, respectively, from the control group. Adult animals showed only a minor increase in brain and plasma 5-HT levels. In young animals, pretreatment with p-CPA (a 5-HT synthesis inhibitor) and indomethacin (a prostaglandin synthesis inhibitor) prevented the FS induced increase in BBB permeability and 5-HT levels. Destruction of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the breakdown of the BBB and attenuated the brain 5-HT level without affecting the plasma 5-HT. Cyproheptadine, ketanserin (5-HT2 receptor antagonists) and vinblastine (a vesicular transport inhibitor) prevented the increased permeability of the BBB alone. The plasma and brain 5-HT continued to remain high. These observations suggest that (i) 5-HT plays an important role in the breakdown of BBB permeability in FS, (ii) this effect of 5-HT on BBB permeability is mediated by 5-HT2 receptors, and (iii) FS induced increase in BBB permeability is age dependent.
在大鼠模型中，研究了内源性血清素（5-羟色胺，5-HT）是否参与短期强迫游泳（FS）运动后血脑屏障（BBB）的改变。将清醒的幼年（8-9周龄，80-90克）动物在30 +/- 1摄氏度的水温下连续强迫游泳30分钟，分别增加了六个和九个脑区血脑屏障对伊文思蓝白蛋白（EBA）和131I-钠的通透性。在扣带回后部皮质、顶叶、枕叶皮质、小脑蚓部、小脑内外侧皮质和海马背表面观察到EBA染色。除了这些脑区，血脑屏障对131I-钠的通透性还进一步扩展到尾状核、丘脑和下丘脑。成年（24-30周龄，300-400克）动物未出现FS对血脑屏障通透性的这种影响。5-HT测量显示，幼年大鼠血浆和脑内的5-HT分别比对照组大幅增加180%和250%。成年动物脑和血浆5-HT水平仅略有增加。在幼年动物中，用对氯苯丙氨酸（一种5-HT合成抑制剂）和吲哚美辛（一种前列腺素合成抑制剂）预处理可防止FS诱导的血脑屏障通透性和5-HT水平升高。用5,7-二羟色胺（5,7-DHT）破坏血清素能神经元可减少血脑屏障的破坏并降低脑内5-HT水平，但不影响血浆5-HT。赛庚啶、酮色林（5-HT2受体拮抗剂）和长春碱（一种囊泡运输抑制剂）单独可防止血脑屏障通透性增加。血浆和脑内的5-HT仍持续保持高水平。这些观察结果表明：（i）5-HT在FS诱导的血脑屏障通透性破坏中起重要作用；（ii）5-HT对血脑屏障通透性的这种作用由5-HT2受体介导；（iii）FS诱导的血脑屏障通透性增加与年龄有关。
