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MK801 减轻小鼠实验性脊髓创伤压迫模型中的继发性损伤。

MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma.

机构信息

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.

出版信息

BMC Neurosci. 2011 Apr 14;12:31. doi: 10.1186/1471-2202-12-31.

DOI:10.1186/1471-2202-12-31
PMID:21492450
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3094200/
Abstract

BACKGROUND

Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI). The aim of this study was to investigate the neuroprotective effect of dizocilpine maleate, MK801 (2 mg/Kg, 30 min and 6 hours after injury) in a mice model of SCI. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy.

RESULTS

Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis. In this study we clearly demonstrated that administration of MK801 attenuated all inflammatory parameters. In fact 24 hours after injury, the degree of spinal cord inflammation and tissue injury (evaluated as histological score), infiltration of neutrophils, NF-κB activation, iNOS, cytokines levels (TNF-α and IL-1β), neurotrophin expression were markedly reduced by MK801 treatment. Moreover, in a separate set of experiments, we have demonstrated that MK801 treatment significantly improved the recovery of locomotory function.

CONCLUSIONS

Blockade of NMDA by MK801 lends support to the potential importance of NMDA antagonists as therapeutic agents in the treatment of acute spinal cord injury.

摘要

背景

谷氨酸兴奋毒性已被证明在脊髓损伤（SCI）的病理生理学中起有害作用。本研究的目的是研究马来酸地佐环平（dizocilpine maleate），MK801（损伤后 30 分钟和 6 小时，2mg/kg）在 SCI 小鼠模型中的神经保护作用。脊髓损伤通过在 T5-T8 椎板切除术的四个水平上应用血管夹到硬脑膜上来诱导。

结果

小鼠的脊髓损伤导致严重的创伤，其特征为水肿、中性粒细胞浸润和细胞凋亡。在本研究中，我们清楚地表明，MK801 的给药减轻了所有炎症参数。事实上，在损伤后 24 小时，脊髓炎症和组织损伤的程度（评估为组织学评分）、中性粒细胞浸润、NF-κB 激活、iNOS、细胞因子水平（TNF-α和 IL-1β）、神经营养因子表达均明显减少通过 MK801 处理。此外，在一组单独的实验中，我们已经证明 MK801 治疗显著改善了运动功能的恢复。

结论

MK801 阻断 NMDA 支持 NMDA 拮抗剂作为治疗急性脊髓损伤的治疗剂的重要性。

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