A new method to image heme-Fe, total Fe, and aggregated protein levels after intracerebral hemorrhage.
A new method to image heme-Fe, total Fe, and aggregated protein levels after intracerebral hemorrhage.
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DOI：
10.1021/acschemneuro.5b00037
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发表时间：
2015-05-20
影响因子：
5
通讯作者：
Colbourne, Frederick
中科院分区：
文献类型：
--
作者：
Hackett, Mark J.;DeSouza, Mauren;Caine, Sally;Bewer, Brian;Nichol, Helen;Paterson, Phyllis G.;Colbourne, Frederick
脑出血（ICH）是一种毁灭性的中风，导致高死亡率和严重残疾的幸存者。不幸的是，这种损伤的潜在机制尚未完全了解。原发性（机械性）创伤后，继发性退行性事件导致血肿周围区域持续的细胞死亡。氧化应激被认为是这种延迟性损伤的关键原因，这可能是由于游离铁催化的自由基反应。不幸的是，这是很难证明与传统的生化检测，不能区分发生在血肿和血肿周围区的变化。这是一个关键的限制，因为血肿包含因初始出血而严重受损的组织，无法挽救，而血肿周围区域受损较小，但存在继发性退行性事件的风险。这些事件包括由游离Fe介导的氧化应激，推测游离Fe来源于血红蛋白分解。因此，最大限度地减少血红蛋白分解和Fe释放后氧化应激引起的损伤是一个主要的治疗目标。然而，游离铁在ICH发病机制中的作用程度仍不清楚。本研究使用了一种新的成像方法，采用共振拉曼光谱映射的血红蛋白，X射线荧光显微镜映射的总铁，和傅立叶变换红外光谱成像的聚集蛋白质ICH大鼠。这种多模态光谱方法用于准确定义血肿/血肿周围边界，并量化每个区域内的Fe浓度和相对聚集蛋白含量，作为氧化应激的标志物。结果显示，相对于假手术动物（0.22 μg cm−2），血肿（0.90 μg cm−2）中的总铁显著增加，ICH 1天内血肿周围区域（0.32 μ g cm − 2）中存在轻微但显著的铁增加，而非血红蛋白的化学形式。相对于假手术动物（积分带面积0.056 Au），血肿（积分带面积0.10 Au）和血肿周围区（积分带面积0.10 Au）内的聚集蛋白水平显著增加，但血肿和血肿周围区之间未观察到聚集蛋白含量的显著差异。该结果表明，Fe的化学形式及其产生自由基的能力可能是比组织的总Fe含量更关键的组织损伤预测因子。此外，本文描述了一种新的方法，共定位非血红素铁和聚集的蛋白质在周围血肿区后，脑出血，该领域的一个显着的方法进步。
An intracerebral hemorrhage (ICH) is a devastating stroke that results in high mortality and significant disability in survivors. Unfortunately, the underlying mechanisms of this injury are not yet fully understood. After the primary (mechanical) trauma, secondary degenerative events contribute to ongoing cell death in the peri-hematoma region. Oxidative stress is thought to be a key reason for this delayed injury, which is likely due to free-Fe-catalyzed free radical reactions. Unfortunately, this is difficult to prove with conventional biochemical assays that fail to differentiate between alterations that occur within the hematoma and peri-hematoma zone. This is a critical limitation, as the hematoma contains tissue severely damaged by the initial hemorrhage and is unsalvageable, whereas the peri-hematoma region is less damaged but at risk from secondary degenerative events. Such events include oxidative stress mediated by free Fe presumed to originate from hemoglobin breakdown. Therefore, minimizing the damage caused by oxidative stress following hemoglobin breakdown and Fe release is a major therapeutic target. However, the extent to which free Fe contributes to the pathogenesis of ICH remains unknown. This investigation used a novel imaging approach that employed resonance Raman spectroscopic mapping of hemoglobin, X-ray fluorescence microscopic mapping of total Fe, and Fourier transform infrared spectroscopic imaging of aggregated protein following ICH in rats. This multimodal spectroscopic approach was used to accurately define the hematoma/peri-hematoma boundary and quantify the Fe concentration and the relative aggregated protein content, as a marker of oxidative stress, within each region. The results revealed total Fe is substantially increased in the hematoma (0.90 μg cm−2), and a subtle but significant increase in Fe that is not in the chemical form of hemoglobin is present within the peri-hematoma zone (0.32 μg cm−2) within 1 day of ICH, relative to sham animals (0.22 μg cm−2). Levels of aggregated protein were significantly increased within both the hematoma (integrated band area 0.10 AU) and peri-hematoma zone (integrated band area 0.10 AU) relative to sham animals (integrated band area 0.056 AU), but no significant difference in aggregated protein content was observed between the hematoma and peri-hematoma zone. This result suggests that the chemical form of Fe and its ability to generate free radicals is likely to be a more critical predictor of tissue damage than the total Fe content of the tissue. Furthermore, this article describes a novel approach to colocalize nonheme Fe and aggregated protein in the peri-hematoma zone following ICH, a significant methodological advancement for the field.
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影响因子：
5.7
作者：
Leskovjan AC;Kretlow A;Lanzirotti A;Barrea R;Vogt S;Miller LM
通讯作者：
Miller LM
DOI：
10.1039/c2mt20052j
发表时间：
2012-08
期刊：
Metallomics : integrated biometal science
影响因子：
--
作者：
Bourassa MW;Miller LM
通讯作者：
Miller LM
影响因子：
3
作者：
Chwiej, Joanna;Adamek, Dariusz;Lankosz, Marek
通讯作者：
Lankosz, Marek
影响因子：
5.7
作者：
Kastyak-Ibrahim, M. Z.;Nasse, M. J.;Gough, K. M.
通讯作者：
Gough, K. M.
影响因子：
3.2
作者：
Liu, Shuo;Grigoryan, Mher Mahoney;Fisher, Mark J.
通讯作者：
Fisher, Mark J.