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DARPP-32 to Quantify Intracerebral Hemorrhage-Induced Neuronal Death in Basal Ganglia

机译:DARPP-32量化基底神经节脑出血引起的神经元死亡

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摘要

Quantification of acute brain injury in basal ganglia is essential for mechanistic and therapeutic studies in experimental intracerebral hemorrhage (ICH). Using conventional counting of degenerating cells based on morphological or immunohistochemical criteria, it is hard to define the boundary of the whole lesion area. Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) is a cytosolic protein highly enriched in medium-sized spiny neurons of the striatum. We developed new methods for quantifying lesion area by detecting the difference of the DARPP-32 negative area and the hematoma clot and by measuring DARPP-32 protein level for semi-qualification in rat model of ICH. We found that DARPP-32-negative area around the hematoma was present at day 1, peaked at day 3, and decreased at day 14 after ICH, a time course paralleled by DARPP-32 Western blots. The DARPP-32-negative area matched well with the necrotic area determined using propidium iodide. Treatment with an iron chelator, deferoxamine, attenuated the ICH-induced reduction in DARPP-32 protein levels. These results suggest that DARPP-32 is a simple and quantifiable indicator of ICH-induced neuronal death in basal ganglia.
机译:量化基底神经节急性脑损伤对于实验性脑出血(ICH)的机制和治疗研究至关重要。使用基于形态学或免疫组织化学标准的退化细胞的常规计数,很难确定整个病变区域的边界。多巴胺和cAMP调节的磷蛋白Mr 32 kDa(DARPP-32)是一种细胞质蛋白,高度富含纹状体的中型棘状神经元。我们通过检测DARPP-32阴性区域与血肿凝块的差异以及通过测量DARPP-32蛋白水平以用于ICH大鼠模型的半鉴定,开发了定量病变区域的新方法。我们发现血肿周围的DARPP-32阴性区域在ICH后第1天出现,在ICH后第3天达到峰值,并在第14天减少,这是一个与DARPP-32 Western印迹平行的时间过程。 DARPP-32阴性区域与使用碘化丙啶测定的坏死区域很好地匹配。用铁螯合剂去铁胺处理可减轻ICH诱导的DARPP-32蛋白水平降低。这些结果表明,DARPP-32是ICH诱导的基底节神经元死亡的简单且可量化的指标。

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  • 来源
    《Translational Stroke Research》 |2013年第1期|130-134|共5页
  • 作者单位

    Department of Neurosurgery University of Michigan">(1);

    Department of Neurology The First Hospital of Jilin University">(2);

    Department of Neurosurgery University of Michigan">(1);

    Department of Neurosurgery University of Michigan">(1);

    Department of Neurology The First Hospital of Jilin University">(2);

    Department of Neurosurgery University of Michigan">(1);

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    DARPP-32; Intracerebral hemorrhage; Iron; Neuronal death;

    机译:DARPP-32;脑出血;铁;神经元死亡;

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