Microglial reactions after subcutaneous formalin injection into the rat hind paw

Microglial reactions after subcutaneous formalin injection into the rat hind paw
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DOI:
10.1016/s0006-8993(99)01186-5
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发表时间:
1999-04-17
期刊:
影响因子:
2.9
通讯作者:
Maixner, W
Maixner, W
中科院分区:
医学3区
文献类型:
--
作者:
Fu, KY;Light, AR;Maixner, W

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周围神经损伤后,初级传入投射区的小胶质细胞被激活和增殖。然而,伤害性刺激刺激周围神经的感受野是否会激活脊髓中的小胶质细胞,目前尚不清楚。本研究旨在研究腰段脊髓和脑干小胶质细胞对强直伤害性刺激的反应。雄性SD大鼠32只,右后掌足底皮下注射5%福尔马林(50亩L),24只大鼠注射50亩L生理盐水作为对照。分别于注射后0、2、4、8小时和1、3、7、14、28天测定腰段脊髓和脑干对补体受体C3bi(单抗OX-42)和主要组织相容性复合体LI(单抗OX-6)的免疫反应性。注射福尔马林后1~3d,OX-42-IR小胶质细胞在同侧脊髓背角内侧和脑干松质核内呈定性和定量增加,7d达高峰。OX-6阳性细胞散在分布于脊髓灰质和白质,但脊髓两侧及福尔马林注射组与对照组无明显差异。这是首次有报道称,将福尔马林注射到大鼠的后爪可以诱导脊髓和脑干中的小胶质细胞激活。虽然我们还没有确定这些反应是由伤害性感受器活动、外周炎症还是初级传入和/或中枢神经元的变性引起的,但该方法提供了一个简单、有效和稳定的动物模型,将允许未来研究小胶质细胞激活的机制及其病理生理后果。(C)1999 Elsevier Science B.V.保留所有权利。
Microglia in primary afferent projection territories are activated and proliferate after peripheral nerve injury. However, it is not known whether stimulation of peripheral nerves by noxious stimuli applied to their receptive fields activates microglial cells in the spinal cord. This study was designed to investigate the response of microglia in the lumbar spinal cord and in the brainstem to a tonic noxious stimulus. Thirty-two male Sprague-Dawley rats received subcutaneous injections of 5% formalin (50 mu l) into the plantar surface of the right hind paw, and 24 rats were injected with 50 mu l saline as a control. The lumbar spinal cord and brainstem were evaluated for immunoreactivity (IR) to complement receptor C3bi (monoclonal antibody OX-42) and major histocompatibility complex class LI (monoclonal antibody OX-6) on postinjection hours 0, 2, 4 and 8 and days 1, 3, 7, 14 and 28. A qualitative and quantitative increase of OX-42-IR microglial cells were observed in the medial portion of the dorsal horn and in the gracile nucleus of the brainstem on the side ipsilateral to the formalin injection, starting on days 1-3 and peaking on day 7 postinjection. OX-6-positive cells were scattered both in gray and white matter, but no difference was detected between the two sides of the spinal cord or between formalin-injected and control animals. This is the first study that reports that subcutaneous injection of formalin into the rat's hind paw induces microglial activation in the spinal cord as well as in the brainstem. Although we have not determined whether these responses result from nociceptor activity, peripheral inflammation, or degeneration of primary afferents and/or central neurons, this method provides a simple, effective and stable animal model that will permit the future study of the mechanisms that contribute to microglial activation and its pathophysiological consequences. (C) 1999 Elsevier Science B.V. All rights reserved.