Dysregulation in myelination mediated by persistent neuroinflammation: possible mechanisms in chemotherapy-related cognitive impairment.
Dysregulation in myelination mediated by persistent neuroinflammation: possible mechanisms in chemotherapy-related cognitive impairment.
复制标题
DOI：
10.1016/j.bbi.2013.07.175
复制
发表时间：
2014-01
影响因子：
15.1
通讯作者：
Woods, Julie
中科院分区：
文献类型：
--
作者：
Briones, Teresita L.;Woods, Julie
认知障碍通常被报道为化疗的结果，并且对癌症患者的日常生活有相当大的影响。因此，有必要清楚地了解这一现象及其潜在的机制。在本研究中，我们研究了神经炎症和髓鞘形成在化疗相关认知障碍中的作用。采用雌性sd大鼠（12月龄），共52只，13只/组。大鼠随机分为化疗组和生理盐水对照组。给予环磷酰胺、甲氨蝶呤、5-氟尿嘧啶（CMF）联合用药，每周1次，连用4周。对照组大鼠给予等体积生理盐水。每组动物进一步随机接受环氧化酶（COX-2）抑制剂NS-393，以阻断炎症反应或媒介。NS-398以10 mg/Kg的剂量腹腔注射，等量生理盐水（对照品）腹腔注射。NS-398和对照体在第一次CMF给药后1小时注射，然后每天给药28天，然后在Y迷宫中进行实验。我们的数据显示：(1)CMF导致炎症介质IL-1β、TNF-α和COX-2水平升高，抗炎细胞因子IL-10水平下降；(2) CMF引起的认知功能障碍和神经炎症在治疗结束后持续4周；(3) NS-398减轻cmf诱导的神经炎症及对髓磷脂和认知障碍的影响。这些发现提示神经炎症参与了cmf诱导的髓磷脂和髓鞘形成的改变以及认知障碍。
Cognitive impairment is commonly reported as a consequence of chemotherapy and can have considerable impact on everyday life on cancer patients. Thus, it is imperative to have a clear understanding of this phenomenon and the underlying mechanism involved. In the present study we examined the role of neuroinflammation and myelination in chemotherapy-related cognitive impairment. Female Sprague-Dawley rats (12-months old) were used in the study (total n=52, 13rats/group). Rats were randomly assigned to either the chemotherapy or saline control group. The drug combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was given i.p. once a week for 4 weeks. Rats in the control group received normal saline of equal volume. Animals from each group were further randomized to receive either: cyclooxygenase (COX-2) inhibitor, NS-393, to block the inflammatory response or vehicle. NS-398 was given at 10 mg/Kg i.p. and equal volume of saline (vehicle) was injected i.p. as vehicle. Both NS-398 and vehicle were injected one hour after the first CMF dose and then given daily for 28 days then rats were tested in the Y maze. Our data showed that: (1) CMF led to the increase in the levels of inflammatory mediators IL-1β, TNF-α, and COX-2 while levels of the anti-inflammatory cytokine IL-10 decreased; (2) cognitive impairment and neuroinflammation resulting from CMF persisted 4 weeks after the treatment ended; and (3) administration of NS-398 attenuated CMF-induced neuroinflammation and effects on myelin and cognitive impairment. These findings suggest the involvement of neuroinflammation in CMF-induced changes in myelin and myelination, and cognitive impairment.
登录
查看更多内容
影响因子：
4
作者：
Janelsins MC;Kohli S;Mohile SG;Usuki K;Ahles TA;Morrow GR
通讯作者：
Morrow GR
影响因子：
4.8
作者：
de Ruiter, Michiel B.;Reneman, Liesbeth;Schagen, Sanne B.
通讯作者：
Schagen, Sanne B.
DOI：
10.1158/1078-0432.ccr-09-1227
发表时间：
2009-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kesler SR;Bennett FC;Mahaffey ML;Spiegel D
通讯作者：
Spiegel D
影响因子：
2.5
作者：
Lu, Po H.;Lee, Grace J.;Bartzokis, George
通讯作者：
Bartzokis, George
影响因子：
3.1
作者：
Ahles, Tim A;Saykin, Andrew J
通讯作者：
Saykin, Andrew J