NEUROGENICALLY MEDIATED LEAKAGE OF PLASMA-PROTEIN OCCURS FROM BLOOD-VESSELS IN DURA-MATER BUT NOT BRAIN
NEUROGENICALLY MEDIATED LEAKAGE OF PLASMA-PROTEIN OCCURS FROM BLOOD-VESSELS IN DURA-MATER BUT NOT BRAIN
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DOI：
10.1523/jneurosci.07-12-04129.1987
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发表时间：
1987-12-01
影响因子：
5.3
通讯作者：
MOSKOWITZ, MA
中科院分区：
文献类型：
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作者：
MARKOWITZ, S;SAITO, K;MOSKOWITZ, MA
本文建立了一种简便、可靠、灵敏的~（125）I-BSA静脉注射法检测化学、电或免疫刺激后大鼠和豚鼠硬脑膜血浆蛋白外渗的方法。在静脉注射1 μ mol/kg辣椒素后，在盐水灌注的大鼠的硬脑膜和结膜中注意到外渗的125 I-BSA或伊文思蓝，但在颞肌中未观察到外渗。辣椒素诱导的外渗是由无髓鞘和小的有髓鞘纤维介导的，因为在新生时通过辣椒素预处理（50 mg/kg）破坏这些纤维的成年动物中没有发生渗漏。电刺激大鼠三叉神经节后，同侧硬脑膜、眼睑、唇和牙龈粘膜及口鼻部的伊文思蓝和125 I-BSA含量增加。这种增加也是C纤维依赖性的。在血管周围传入纤维中所含的肽中，静脉注射P物质（SP）和神经激肽A（NKA），而不是降钙素基因相关肽，引起大鼠硬脑膜和结膜的剂量依赖性外渗。新生儿辣椒素预处理并没有减弱SP-也没有NKA-诱导的影响，在硬脑膜，实际上增加了结膜外渗。对正常成年大鼠或在新生儿时用辣椒素预处理的成年大鼠静脉注射5-HT或缓激肽，会增加硬脑膜和结膜中125 I-BSA的水平。组胺和前列腺素E2，另一方面，引起蛋白质渗漏结膜，但不是在硬脑膜的大鼠，然而，组胺诱导外渗在硬脑膜的豚鼠。卵清蛋白的挑战，以前致敏的豚鼠产生显着的硬膜和结膜外渗，这是显着减少联合H1和H2组胺受体阻滞剂。辣椒素致密化减少了58%的硬脑膜和30%的结膜渗透性的增加，这一发现表明C纤维的参与。然而，这种减少在统计学上并不显著。在化学、电或免疫刺激后，也未在局部应用辣椒素至软膜表面或注射至大鼠皮质后的脑中观察到外渗。神经源性介导的硬脑膜血浆外渗的血管性头痛的病理生理的影响进行了讨论。
Utilizing 125I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea-pigs following chemical, electrical, or immunological stimulation. Extravasated 125I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 .mu.mol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and 125I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of 125I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea-pigs. Ovalbumin challenge to previously sensitized guinea-pigs produced marked dural and conjunctival extravasation, which was significantly reduced by combined H1 and H2 histamine receptor blockade. Participation of C fibers was suggested by the finding that capsaicin densitization diminished the increase in permeability by 58% in the dura and 30% in the conjunctiva. This reduction was not statistically significant, however. Extravasation was not observed in the brain following chemical, electrical, or immunological stimulation nor following topical application of capsaicin to the pial surface or injection into the cortex of rats. The implications of neurogenically mediated dural plasma extravasation for the pathophysiology of vascular head pain are discussed.