Propentofylline attenuates allodynia, glial activation and modulates GABAergic tone after spinal cord injury in the rat
Propentofylline attenuates allodynia, glial activation and modulates GABAergic tone after spinal cord injury in the rat
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DOI：
10.1016/j.pain.2008.01.021
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发表时间：
2008-08-31
期刊：
影响因子：
7.4
通讯作者：
Hulsebosch, Claire E.
中科院分区：
文献类型：
--
作者：
Gwak, Young Seob;Crown, Eric D.;Hulsebosch, Claire E.
在这项研究中，我们评估了甲基黄嘌呤衍生物丙戊茶碱是否存在。通过调节脊髓损伤 (SCI) 后脊髓背角中的谷氨酸脱羧酶 (GAD)65（GABA 合成酶）来调节脊髓盘激活和 GABA 能抑制音。 Sprague-Dawley 大鼠（225-250 g）在 T13 脊柱节段从背侧到腹侧进行单侧脊柱横向损伤。与假手术对照组相比，单侧脊髓损伤的大鼠在腰椎增大（L4-L5）中出现强烈的双侧后肢机械异常性疼痛和脊髓宽动态范围（WDR）神经元的过度兴奋。通过鞘内 (i.t.) 施用 GABA 可以减弱这种作用。剂量依赖性（0.01、0.1、0.5μg）。 Western blotting和免疫组织化学数据表明，SCI后腰椎背角（L4/5）两侧GAD（65）蛋白的表达水平显着降低（p < 0.05）。此外，与假手术对照组相比，星形胶质细胞和小胶质细胞分别通过增加的体细胞面积和腰椎背角两侧的 GFAP 和 CD11b 增加来确定体细胞肥大（p < 0.05）。鞘内注射丙戊茶碱 (PPF 10 mM) 显着减轻星形细胞和小胶质细胞体肥大以及机械异常性疼痛 (1) < 0.05)。此外，蛋白质印迹和免疫组织化学数据表明，它。 PPF 治疗显着阻止 SCI 后腰椎背角两侧 GAD(65) 表达的下降 (1) < 0.05)。综上所述。我们目前的数据表明，丙戊茶碱通过调节脊髓损伤后的 GAD(65) 蛋白表达来调节神经胶质细胞活化和 GABA 能抑制性孤独。 (C) 2005 年由 Elsevier B.V. 代表国际疼痛研究协会出版。
In this study, we evaluated wether propentofylline, a methylxanthine derivative. modulates spinal dial activation and GABAergic inhibitory tone by modulation of glutamic acid decarboxylase (GAD)65, the GABA synthase enzyme, in the spinal dorsal horn following spinal cord injury (SCI). Sprague-Dawley rats (225-250 g) were given a unilateral spinal transverse injury, from dorsal to ventral, at the T13 spinal segment. Unilateral spinal injured rats developed robust bilateral hindlimb mechanical allodynia and hyperexcitability of spinal wide dynamic range (WDR) neurons in the lumbar enlargement (L4-L5) compared to sham controls. which was attenuated by intrathecal (i.t.) administration of GABA. dose-dependently (0.01, 0.1. 0.5 mu g). Western blotting and immunohistochemical data demonstrated that the expression level of GAD(65) protein significantly decreased on both sides of the Iumbar dorsal horn (L4/5) after SCI (p < 0.05). In addition, astrocytes and microglia showed soma hypertrophy as determined by increased soma area and increased GFAP and CD11b on both sides of the lumbar dorsal horn compared to sham controls, respectively (p < 0.05). Intrathecal treatment with propentofylline (PPF 10 mM) significantly attenuated the astrocytic and microglial soma hypertrophy and mechanical allodynia (1) < 0.05). Additionally, the Western blotting and immunohistochemistry data demonstrated that i.t. treatment of PPF significantly prevented the decrease of GAD(65) expression in both sides of the lumbar dorsal horn following SCI (1) < 0.05). In conclusion. our present data demonstrate that propentofylline modulates glia activation and GABAergic inhibitory lone by modulation of GAD(65) protein expression following spinal cord injury. (C) 2005 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.