Ligation of the jugular veins does not result in brain inflammation or demyelination in mice.
Ligation of the jugular veins does not result in brain inflammation or demyelination in mice.
复制标题
DOI：
10.1371/journal.pone.0033671
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen JW
中科院分区：
文献类型：
--
作者：
Atkinson W;Forghani R;Wojtkiewicz GR;Pulli B;Iwamoto Y;Ueno T;Waterman P;Truelove J;Oklu R;Chen JW
另一种假说认为慢性脑脊髓静脉功能不全(CCSVI)是多发性硬化症(MS)的潜在原因。我们的目的是在受控动物模型中评估这一假说的有效性。动物实验得到了机构动物护理委员会的批准。结扎双侧颈静脉(n = 20)，结扎后观察6个月。以假手术小鼠(n = 15)和实验性自身免疫性脑脊髓炎小鼠(n = 8)作为阴性对照和阳性对照。用CT静脉造影和99mTc-地塞美他嗪评价动物的结构和血流动力学变化。进行成像以评估血脑屏障(BBB)破坏和神经炎症的迹象。采用流式细胞术和组织病理学方法检测炎性细胞数量和脱髓鞘情况。~(99m)Tc99m显像示颈静脉引流结构改变(狭窄、侧支)和脑血流动力学障碍(p = 0.024)。在JVL小鼠中，Gd核磁共振和屏障分子的免疫荧光成像没有显示血脑屏障破裂的证据(p = 0.58)。髓过氧化物酶、基质金属蛋白酶和蛋白酶分子成像没有显示神经炎症增加的迹象(均为p>；0.05)。流式细胞术和组织病理学也没有发现炎性细胞浸润或群体转移的增加。没有发现脱髓鞘的证据，小鼠仍然没有临床症状。尽管结构和血流动力学发生了变化，但与假手术组相比，JVL组在血脑屏障通透性、神经炎症、脱髓鞘或临床体征方面没有发现变化。因此，我们的小鼠模型不支持CCSVI是多发性硬化症等脱髓鞘疾病的原因。
An alternative hypothesis has been proposed implicating chronic cerebrospinal venous insufficiency (CCSVI) as a potential cause of multiple sclerosis (MS). We aimed to evaluate the validity of this hypothesis in a controlled animal model. Animal experiments were approved by the institutional animal care committee. The jugular veins in SJL mice were ligated bilaterally (n = 20), and the mice were observed for up to six months after ligation. Sham-operated mice (n = 15) and mice induced with experimental autoimmune encephalomyelitis (n = 8) were used as negative and positive controls, respectively. The animals were evaluated using CT venography and 99mTc-exametazime to assess for structural and hemodynamic changes. Imaging was performed to evaluate for signs of blood-brain barrier (BBB) breakdown and neuroinflammation. Flow cytometry and histopathology were performed to assess inflammatory cell populations and demyelination. There were both structural changes (stenosis, collaterals) in the jugular venous drainage and hemodynamic disturbances in the brain on Tc99m-exametazime scintigraphy (p = 0.024). In the JVL mice, gadolinium MRI and immunofluorescence imaging for barrier molecules did not reveal evidence of BBB breakdown (p = 0.58). Myeloperoxidase, matrix metalloproteinase, and protease molecular imaging did not reveal signs of increased neuroinflammation (all p>0.05). Flow cytometry and histopathology also did not reveal increase in inflammatory cell infiltration or population shifts. No evidence of demyelination was found, and the mice remained without clinical signs. Despite the structural and hemodynamic changes, we did not identify changes in the BBB permeability, neuroinflammation, demyelination, or clinical signs in the JVL group compared to the sham group. Therefore, our murine model does not support CCSVI as a cause of demyelinating diseases such as multiple sclerosis.
登录
查看更多内容
影响因子：
5.7
作者：
McCann CM;Waterman P;Figueiredo JL;Aikawa E;Weissleder R;Chen JW
通讯作者：
Chen JW
影响因子：
5.2
作者：
Querol, M;Chen, JW;Bogdanov, A
通讯作者：
Bogdanov, A
影响因子：
15.9
作者：
Swirski, Filip K.;Wildgruber, Moritz;Nahrendorf, Matthias
通讯作者：
Nahrendorf, Matthias
影响因子：
14.5
作者：
Kieseier, BC;Kiefer, R;Hartung, HP
通讯作者：
Hartung, HP
影响因子：
6
作者：
Brück, W
通讯作者：
Brück, W