Sharma H S, Olsson Y, Dey P K
Laboratory of Neuropathology, Institute of Pathology, University Hospital, Uppsala, Sweden.
Brain Res. 1990 May 28;517(1-2):215-23. doi: 10.1016/0006-8993(90)91029-g.
Plasma serotonin (5-HT) was elevated by an intravenous infusion of this amine into urethane-anaesthetized rats and the concentration approximated that present in various neurological diseases and mental abnormalities. An infusion of 10 micrograms per kg body weight for 10 min significantly increased blood-brain barrier (BBB) permeability to Evans blue and 131I-sodium measured in whole brain. Regional BBB determinations with labelled 131I-sodium showed that the permeability to this compound was increased in the cerebral cortex, hippocampus, caudate nucleus, hypothalamus, colliculus and the cerebellum but not in the pons and the medulla oblongata. Regional blood flow was reduced in the same parts which showed BBB abnormality tested with 125I-labeled microspheres. Pretreatment with cyproheptadine, a 5-HT2 receptor antagonist, prevented the BBB increase and the regional blood flow was near normal values. Similar effects were obtained with indomethacin, a prostaglandin synthesis inhibitor. Vinblastine, known to influence vesicular transport, eliminated extravasation of the tracers but the regional blood flow remained depressed. A hypothesis is put forward that serotonin after binding to its receptor in the cerebral vessels stimulates prostaglandin which either directly or by means of cyclic adenosine monophosphate causes an increased vesicular transport across the endothelial cells and thus an extravasation of tracer substances in the brain. Obviously, this form of exudation can be influenced by pharmacological means.
通过向氨基甲酸乙酯麻醉的大鼠静脉输注这种胺，血浆5-羟色胺（5-HT）升高，其浓度接近各种神经疾病和精神异常中存在的浓度。以每千克体重10微克的剂量输注10分钟，可显著增加血脑屏障（BBB）对全脑中伊文思蓝和131I-钠的通透性。用标记的131I-钠进行的区域血脑屏障测定表明，大脑皮质、海马体、尾状核、下丘脑、丘和小脑中该化合物的通透性增加，而脑桥和延髓中则没有增加。用125I标记的微球测试显示，血脑屏障异常的相同部位区域血流减少。用5-HT2受体拮抗剂赛庚啶预处理可防止血脑屏障通透性增加，区域血流接近正常值。用前列腺素合成抑制剂吲哚美辛也得到了类似的效果。已知长春碱会影响囊泡运输，它可消除示踪剂的外渗，但区域血流仍处于降低状态。有人提出一种假说，即血清素与脑血管中的受体结合后会刺激前列腺素，前列腺素要么直接，要么通过环磷酸腺苷导致囊泡跨内皮细胞运输增加，从而使示踪物质在脑中渗出。显然，这种渗出形式可受药理学方法影响。
