Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury.
Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury.
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DOI：
10.1371/journal.pone.0030012
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xu XM
中科院分区：
文献类型：
--
作者：
Walker CL;Walker MJ;Liu NK;Risberg EC;Gao X;Chen J;Xu XM
原发性脊髓损伤后的继发性损伤使病理学超出了最初的创伤部位，有效的治疗对于最大限度地恢复解剖和功能至关重要。双过氧钒化合物已在几种中枢神经系统损伤/疾病模型中证明了神经保护作用，然而，没有机制与脊髓创伤后双过氧钒治疗的这种神经保护有关。本研究的目的是评估急性双过氧钒治疗对颈椎单侧挫伤性脊髓损伤后神经保护和功能恢复的影响，并研究该化合物作用的潜在机制。建立了两个大鼠实验组，以1）使用新的食物操作试验评估化合物双过氧（吡啶）钒钾每天两次7天治疗对熟练前肢活动的长期恢复，以及损伤后6周的神经保护作用，和2）阐明损伤后药物作用的急性机制联系。SCI后1天进行免疫荧光和Western印迹以评估细胞信号传导，并利用组织化学和前肢功能分析来评估损伤后6周的神经保护和恢复。双过氧钒通过减少运动神经元死亡、增加组织保留和最小化大鼠空洞形成来促进显著的神经保护。还观察到在治疗进食评估期间前肢功能能力增强。此外，双过氧钒显著增强下游Akt和雷帕霉素信号传导的哺乳动物靶点，并降低自噬活性，表明抑制10号染色体上缺失的磷酸酶和张力蛋白同源物是创伤性脊髓损伤后双过氧钒作用的潜在机制。总体而言，本研究证明了临床适用的药理学治疗在脊髓损伤后快速启动神经保护的有效性，并阐明了其作用中涉及的信号传导。
Secondary damage following primary spinal cord injury extends pathology beyond the site of initial trauma, and effective management is imperative for maximizing anatomical and functional recovery. Bisperoxovanadium compounds have proven neuroprotective effects in several central nervous system injury/disease models, however, no mechanism has been linked to such neuroprotection from bisperoxovanadium treatment following spinal trauma. The goal of this study was to assess acute bisperoxovanadium treatment effects on neuroprotection and functional recovery following cervical unilateral contusive spinal cord injury, and investigate a potential mechanism of the compound's action. Two experimental groups of rats were established to 1) assess twice-daily 7 day treatment of the compound, potassium bisperoxo (picolinato) vanadium, on long-term recovery of skilled forelimb activity using a novel food manipulation test, and neuroprotection 6 weeks following injury and 2) elucidate an acute mechanistic link for the action of the drug post-injury. Immunofluorescence and Western blotting were performed to assess cellular signaling 1 day following SCI, and histochemistry and forelimb functional analysis were utilized to assess neuroprotection and recovery 6 weeks after injury. Bisperoxovanadium promoted significant neuroprotection through reduced motorneuron death, increased tissue sparing, and minimized cavity formation in rats. Enhanced forelimb functional ability during a treat-eating assessment was also observed. Additionally, bisperoxovanadium significantly enhanced downstream Akt and mammalian target of rapamycin signaling and reduced autophagic activity, suggesting inhibition of the phosphatase and tensin homologue deleted on chromosome ten as a potential mechanism of bisperoxovanadium action following traumatic spinal cord injury. Overall, this study demonstrates the efficacy of a clinically applicable pharmacological therapy for rapid initiation of neuroprotection post-spinal cord injury, and sheds light on the signaling involved in its action.
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影响因子：
6.1
作者：
Kanno, Haruo;Ozawa, Hiroshi;Itoi, Eiji
通讯作者：
Itoi, Eiji
影响因子：
3
作者：
Kanno, Haruo;Ozawa, Hiroshi;Itoi, Eiji
通讯作者：
Itoi, Eiji
影响因子：
3.5
作者：
Dahia, PLM;Aguiar, RCT;Eng, C
通讯作者：
Eng, C
正常成年大鼠脑中 PTEN 的差异表达及缺血大脑皮层中 PTEN 和 p-Akt 的上调
DOI：
10.1002/ar.20834
发表时间：
2009-04-01
影响因子：
2
作者：
Cai, Qi-Yan;Chen, Xing-Shu;Yao, Zhong-Xiang
通讯作者：
Yao, Zhong-Xiang
影响因子：
14.5
作者：
Han, Shu;Arnold, Sheila A.;Hagg, Theo
通讯作者：
Hagg, Theo