中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (1): 100-106.doi: 10.4103/1673-5374.243715

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

以反复炎症汤刺激清醒恒河猴硬脑膜建立复发性偏头痛大动物模型

  

  • 出版日期:2019-01-15 发布日期:2019-01-15
  • 基金资助:

    中国国家自然科学基金项目（81500959）

A novel large animal model of recurrent migraine established by repeated administration of inflammatory soup into the dura mater of the rhesus monkey

Ning Chen1, Wei Su1, 2, Shu-Hui Cui1, Jian Guo1, Jia-Chuan Duan3, Hong-Xia Li3, Li He1   

  1. 1 Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
    2 Department of Science & Technology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
    3 National Chengdu Center for Safety Evaluation of Traditional Chinese Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
  • Online:2019-01-15 Published:2019-01-15
  • Contact: Li He, PhD, heli2003new@126.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81500959 (to NC).

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摘要：

目前基于三血管系统激活假说的几种偏头痛动物模型已被广泛接受，但主要基于啮齿类低等哺乳动物，且大多数模型只能接受一次刺激。实验通过留置导管将前列腺素E2(0.2 mM)、血清素(2 mM)、缓激肽(2 mM)和组胺(2 mM)组成的炎症汤(10 µL)注入清醒猕猴硬脑膜，从第8天开始，每3d注射一次，连续注射6次，建立硬脑膜神经源性炎症模型。然后进行行为学评估，并以免疫组色染色法检测三叉神经系统和参与疼痛加工的多个脑区中c-fos、神经型一氧化氮合酶和降钙素基因相关肽的免疫阳性反应。发现3只(3/4)大鼠出现运动行为减少，且2只在刺激期出现口鼻分泌物增加，三叉神经核尾、丘脑、下丘脑、中脑、脑桥及其他疼痛感知相关脑区中神经型一氧化氮合酶和降钙素基因相关肽的免疫阳性反应增加。表明以反复炎症汤刺激硬脑膜可激活三叉血管系统，使清醒恒河猴出现偏头痛样病理变化及异常行为。

orcid: 0000-0002-2034-1027(Li He)

关键词: 偏头痛, 恒河猴, 神经原性炎症, c-fos, 神经型一氧化氮合酶, 降钙素基因相关肽, 三叉神经系统, 行为, 免疫组化, 神经再生

Abstract:

Several animal models of migraine have been established, and those based on trigeminovascular system activation are widely accepted. How¬ever, most of these models have been established on lower animals, such as rodents, and involve only a single administration of a noxious stimulus. In this study, an inflammatory soup (10 μL), consisting of prostaglandin E2 (0.2 mM), serotonin (2 mM), bradykinin (2 mM) and histamine (2 mM), was injected into the dura mater of conscious rhesus monkeys through an indwelling catheter. The infusion started on day 8 and was repeated every 3 days, for a total of six administrations, to induce neurogenic inflammation. We performed behavioral assessments and measured the expression of the oncogene c-fos, neuronal nitric oxide synthase (nNOS) and calcitonin gene related peptide (CGRP) in the trigeminal system and in multiple brain regions involved in pain processing by immunohistochemical staining. Compared with monkeys in the control group, three of the four animals in the inflammatory soup group displayed decreased motor behaviors, and two showed increased ipsilateral nose and mouth secretions during the stimulus period. Higher expression levels of c-fos, nNOS and CGRP were found in various brain areas of experimental animals compared with controls, including the trigeminal nucleus caudalis, thalamus, hypothalamus, midbrain, pons and other areas involved in pain perception. These results suggest that repeated inflammatory soup stimulation of the dura activates the trigeminovascular system and produces migraine-like pathological changes and abnormal behaviors in conscious rhesus monkeys.

Key words: nerve regeneration, migraine, rhesus monkey, neurogenic inflammation, cellular oncogene fos, neuronal nitric oxide synthase, calcitonin gene related peptide, trigeminal system, behavior, immunohistochemistry, neural regeneration