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首页> 外文期刊>European Journal of Nuclear Medicine and Molecular Imaging >Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins.
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Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins.

机译:利鲁唑保护亨廷顿病患者免受脑葡萄糖代谢异常和灰质体积损失的影响,并增加神经营养蛋白的产生。

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PURPOSE: Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. METHODS: We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and (18)F-fluoro-2-deoxy-D-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. RESULTS: Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. CONCLUSION: The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD.
机译:目的:亨廷顿病(HD)突变可增加毒性获得功能,从而促进谷氨酸介导的兴奋性毒性。利鲁唑干扰谷氨酸能神经传递,从而降低兴奋性毒性,增强受损的运动神经元中的神经突形成,并增加BDNF(一种保护皮层神经元免受变性的大脑皮质神经营养蛋白)的血清浓度。方法:根据全自动和全自动扫描技术,我们通过MRI和(18)F-氟-2-脱氧-D-葡萄糖(FDG)PET扫描研究了11例接受利鲁唑治疗的患者和12例接受安慰剂治疗的患者在不同大脑区域的代谢和体积差异协议。我们还研究了利鲁唑对外周血生长因子血液水平的影响。结果:与利鲁唑治疗的患者相比,安慰剂治疗的患者在所有皮质区域的灰质比例体积损失和代谢性FDG吸收均显着增加(p <0.05)。与接受利鲁唑治疗的患者相比,接受安慰剂治疗的患者的代谢性FDG摄取率降低与临床评分恶化相关。在安慰剂治疗的患者中,在额叶,顶叶和枕叶皮层中观察到的代谢性FDG摄取的逐渐减少与运动评分的严重程度线性相关,该评分由统一的Huntington疾病评分量表(UHDRS-1)计算。同样,在安慰剂治疗的患者中,大脑皮质额叶和颞叶区域的代谢变化速率与UHDRS-III计算的行为评分恶化呈线性相关。最后,利鲁唑治疗的患者的BDNF和转化生长因子β-1血清水平明显更高。结论:在安慰剂治疗的患者中,代谢性FDG摄取减少与临床评分恶化之间存在线性关系,这表明FDG-PET可能是评估HD脑标志物的有价值的方法。

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