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首页> 外文期刊>CNS neuroscience & therapeutics. >Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
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Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury

机译：在脊髓持续输注肿瘤坏死因子受体2激动剂可改善创伤性挫伤后的恢复

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Aim The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury. Methods EHD2‐sc‐mTNFsubR2/sub, an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6?weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation. Results The activation of TNFR2 protected neurons from glutamate‐mediated excitotoxicity through the activation of phosphoinositide‐3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2‐sc‐mTNFsubR2/sub, but higher levels of neurofilament H and 2′, 3′‐cyclic‐nucleotide 3′‐phosphodiesterase were observed 6?weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation. Conclusion The activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation.
机译：目的TNFR2受体的激活在中枢神经系统的多种病理学中是有益的，这项研究探讨了它是否可以改善脊髓损伤后的恢复过程。方法采用EHD2-sc-mTNF R2 （一种对TNFR2特异性的激动剂）治疗体外暴露于高谷氨酸水平的神经元。在体内，在T9水平对脊髓造成挫伤后立即通过渗透泵将其直接注入脊髓。评估运动行为6周，并分析损伤后的组织（病变大小，RNA和蛋白质表达，细胞死亡）。还测量了对后肢刺激的体感诱发电位。结果TNFR2的激活通过体外磷酸肌醇3激酶γ的激活保护神经元免受谷氨酸介导的兴奋性毒性，并改善了脊髓损伤后动物的运动能力。输注EHD2-sc-mTNF R2 并不会影响损伤的程度，但是在6周后观察到较高水平的神经丝H和2'，3'-环核苷酸3'-磷酸二酯酶受伤。最后，损伤后TNFR2的激活增加了后肢刺激后皮质中记录的神经反应。结论挫伤性损伤后脊髓中TNFR2的激活导致运动增强，皮层对后肢刺激的反应更好。

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