Activation of p-38alpha MAPK contributes to neuronal hyperexcitability in caudal regions remote from spinal cord injury.
Activation of p-38alpha MAPK contributes to neuronal hyperexcitability in caudal regions remote from spinal cord injury.
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DOI：
10.1016/j.expneurol.2009.08.012
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发表时间：
2009-11
影响因子：
5.3
通讯作者：
Hulsebosch, Claire E.
中科院分区：
文献类型：
--
作者：
Gwak, Young S.;Unabia, Geda C.;Hulsebosch, Claire E.
在本研究中，我们检查了 p-38α MAPK 的激活是否调节机械异常性疼痛和神经元过度兴奋，以及丙戊茶碱（PPF，一种神经胶质调节剂）是否调节远离大鼠低胸半切损伤的尾部区域的特异性局部激活的 p-38α MAPK 表达。与假手术对照组相比，T13 脊髓半切会在后爪产生双侧机械异常性疼痛，并诱发（响应机械刺激）腰椎宽动态范围（WDR）神经元的神经元过度兴奋。鞘内和局部施用 SB203580（一种 p-38α MAPK 激活抑制剂）可减弱机械性异常性疼痛和 WDR 神经元的诱发活动，呈剂量依赖性（*p<0.05）；然而，与假对照组相比，自发活动没有显示出显着差异。 T13 脊髓半切后，与假手术对照组相比，腰脊髓浅层和深层背角神经元以及小胶质细胞中磷酸化（激活形式）p-38α MAPK 表达显着增加，但星形胶质细胞中不存在（*p<0.05）。与半切组相比，鞘内应用 PPF 显着减弱了腰脊髓浅表背角神经元 (10 mM) 和小胶质细胞 (1 和 10 mM) 中磷酸化 p-38α MAPK 的表达 (*p<0.05)。总之，我们目前的数据表明，激活的神经元和小胶质细胞而非星形胶质细胞的 p-38α MAPK 有助于维持脊髓损伤后尾部区域的神经元过度兴奋。
In the present study, we examined whether activation of p-38α MAPK modulates mechanical allodynia and neuronal hyperexcitability, and if propentofylline (PPF, a glial modulator) modulates specifically localized activated p-38α MAPK expression in caudal regions remote from a low thoracic hemisection injury in rats. T13 spinal hemisection produces bilateral mechanical allodynia in hindpaws with evoked (in response to mechanical stimuli) neuronal hyperexcitability in lumbar spinal wide dynamic range (WDR) neurons compared to sham controls. The mechanical allodynia and the evoked activity of WDR neurons is attenuated by intrathecal and topical administration of SB203580, an inhibitor of p-38α MAPK activation, dose dependently (*p<0.05); however, the spontaneous activity showed no significant differences compared to sham controls. After T13 spinal hemisection, significantly increased phosphorylated (activated form) p-38α MAPK expression was present in both superficial and deep dorsal horn neurons as well as in microglia, but not in astrocytes, in the lumbar spinal cord compared to sham controls (*p<0.05). Intrathecal application of PPF significantly attenuated the expression of phosphorylated p-38α MAPK in superficial dorsal horn neurons (10 mM) and in microglia (1 and 10 mM) in the lumbar spinal cord compared to the hemisection group (*p<0.05). In conclusion, our present data demonstrate that activated neuronal and microglial, but not astrocytic, p-38α MAPK contributes to the maintenance of neuronal hyperexcitability in caudal regions following spinal cord injury.
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影响因子：
3.3
作者：
Gwak, Y. S.;Hulsebosch, C. E.
通讯作者：
Hulsebosch, C. E.
影响因子：
7.4
作者：
Gwak, Young Seob;Crown, Eric D.;Hulsebosch, Claire E.
通讯作者：
Hulsebosch, Claire E.
影响因子：
7.4
作者：
Raghavendra, V;Tanga, F;DeLeo, JA
通讯作者：
DeLeo, JA
影响因子：
4.7
作者：
Nesic, O;Lee, J;Perez-Polo, JR
通讯作者：
Perez-Polo, JR
影响因子：
2.5
作者：
Lee, IH;Lindqvist, E;Olson, L
通讯作者：
Olson, L