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抑制星形胶质细胞活性可减轻脑出血急性期的后遗症。

Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage.

作者信息

Chiu Cheng-Di, Yao Nai-Wei, Guo Jeng-Hung, Shen Chiung-Chyi, Lee Hsu-Tung, Chiu You-Pen, Ji Hui-Ru, Chen Xianxiu, Chen Chun-Chung, Chang Chen

机构信息

School of Medicine, China Medical University, Taichung, Taiwan.

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.

出版信息

Oncotarget. 2017 Oct 24;8(55):94850-94861. doi: 10.18632/oncotarget.22022. eCollection 2017 Nov 7.

DOI:10.18632/oncotarget.22022
PMID:29212271
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5706917/
Abstract

Neurological deterioration of intracerebral hemorrhage (ICH) mostly occurs within the first 24 hours. Together with the microglia/macrophages (MMΦ), astrocytes are important cell population responsible for many brain injuries but rarely being highlighted in acute stage of ICH. In present study, we induced rats ICH either by collagenase or autologous blood injection. Experimental groups were classified as vehicle or Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3) treatment group ( = 9, each group). MRI assessments after ICH were used to evaluate the hematoma progression and blood-brain barrier (BBB) integrity. The glia cells accumulations were examined by GFAP and Iba1 immunohistochemistry, respectively. Abundant astrocytes but few MMΦ were observed in hyperacute and acute ICH. Upon suppression of astrocyte activity, ICH rats exhibited decreased size of hematoma expansion, less BBB destruction, reduced astrocyte accumulation in perihematomal regions, postponed course of hemoresolution and gain better outcomes. These finding provide evidence that activated astrocytes are crucial cell populations in hyperacute and acute ICH, and their modulation may offer opportunities for novel therapy and patient management.

摘要

脑出血（ICH）的神经功能恶化大多发生在最初24小时内。与小胶质细胞/巨噬细胞（MMΦ）一样，星形胶质细胞是导致多种脑损伤的重要细胞群体，但在ICH急性期很少受到关注。在本研究中，我们通过胶原酶或自体血注射诱导大鼠ICH。实验组分为溶剂对照组或1-（4-（2,3,3-三氯丙烯酰胺）苯基）-5-（三氟甲基）-1H-吡唑-4-羧酸乙酯（Pyr3）治疗组（每组n = 9）。ICH后的MRI评估用于评估血肿进展和血脑屏障（BBB）完整性。分别通过GFAP和Iba1免疫组织化学检查胶质细胞积聚情况。在超急性和急性ICH中观察到大量星形胶质细胞，但MMΦ较少。抑制星形胶质细胞活性后，ICH大鼠血肿扩大体积减小，BBB破坏减轻，血肿周围区域星形胶质细胞积聚减少，血肿溶解过程推迟，预后更好。这些发现证明，活化的星形胶质细胞是超急性和急性ICH中的关键细胞群体，对其进行调节可能为新的治疗方法和患者管理提供机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/b5fcb2040f88/oncotarget-08-94850-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/724537ef9a59/oncotarget-08-94850-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/bb398704692f/oncotarget-08-94850-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/cb83adaaa6ac/oncotarget-08-94850-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/b5fcb2040f88/oncotarget-08-94850-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/724537ef9a59/oncotarget-08-94850-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/bb398704692f/oncotarget-08-94850-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/cb83adaaa6ac/oncotarget-08-94850-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/bdce9cb556a4/oncotarget-08-94850-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3383/5706917/b5fcb2040f88/oncotarget-08-94850-g005.jpg

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