Chronic stress-induced changes in pro-inflammatory cytokines and spinal glia markers in the rat: a time course study.

Chronic stress-induced changes in pro-inflammatory cytokines and spinal glia markers in the rat: a time course study.
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DOI:
10.1159/000342092
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发表时间:
2012
影响因子:
2.4
通讯作者:
Bradesi S
Bradesi S
中科院分区:
医学4区
文献类型:
--
作者:
Golovatscka V;Ennes H;Mayer EA;Bradesi S

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在慢性应激的啮齿动物模型中,脊髓胶质细胞的激活被认为是内脏痛觉过敏的机制之一。为了评估循环细胞因子和血脊髓屏障(BSCB)通透性的变化在脊髓胶质细胞激活中的可能作用,我们研究了外周和脊髓促炎细胞因子以及脊髓和卫星胶质细胞标志物在反复水回避应激(WA)反应中的时间进程。收集对照组大鼠脊髓和背根神经节细胞(DRGs),连续5天每天暴露1小时,连续5天每天暴露1小时,连续10天每天暴露1小时。我们发现,与对照组相比,应激动物循环中的IL-1β和脊髓中的IL-1β、IL-6和肿瘤坏死因子-α具有时间依赖性的变化。我们发现星形胶质细胞标记物GFAP和连接蛋白43在不同时间点在脊髓和背根节标本中的表达发生了变化。最后,Wa与BSCB通透性增加有关。这些发现证实了外周和脊髓免疫标记物在慢性创伤后都发生了改变的概念,并提示应激诱导的外周致炎细胞因子的增加、卫星胶质细胞的变化、BSCB通透性的增加和提示胶质细胞激活的脊髓促炎介质的增加之间可能存在联系。
Spinal glia activation has been proposed as one mechanism underlying visceral hyperalgesia in a rodent model of chronic stress. In order to assess the possible role of changes in circulating cytokines and in blood-spinal cord barrier (BSCB) permeability in spinal glia activation, we studied the time course of peripheral and spinal pro-inflammatory cytokines and of spinal and satellite glia markers in response to repeated water avoidance stress (WA). Spinal cords and dorsal root ganglion cells (DRGs) were collected from control rats, rats exposed to 1-hour WA, or 1-hour WA daily for 5 days or 1-hour WA daily for 10 days. We demonstrated a time-dependent change in circulating IL-1β and spinal IL-1β, IL-6 and TNF-α in stressed animals compared with controls. We found altered expression of the astrocytes marker GFAP and connexin 43 in spinal and DRG samples at different time points. Finally, WA was associated with increased BSCB permeability. These findings confirm the concept that both peripheral and spinal immune makers are altered after chronic WA and suggest a possible link between stress-induced increase of peripheral pro-inflammatory cytokines, changes in satellite glial cells, increased in BSCB permeability and increase in spinal pro-inflammatory mediators suggesting glia activation.
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