Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage.
Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage.
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DOI：
10.18632/oncotarget.22022
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发表时间：
2017-11-07
期刊：
影响因子：
--
通讯作者：
Chang C
中科院分区：
文献类型：
--
作者：
Chiu CD;Yao NW;Guo JH;Shen CC;Lee HT;Chiu YP;Ji HR;Chen X;Chen CC;Chang C
脑出血 (ICH) 的神经功能恶化大多发生在最初 24 小时内。星形胶质细胞与小胶质细胞/巨噬细胞 (MMΦ) 一起是导致许多脑损伤的重要细胞群，但在 ICH 急性期很少被强调。在本研究中，我们通过胶原酶或自体血注射诱导大鼠脑出血。实验组分为媒介物或乙基-1-(4-(2,3,3-三氯丙烯酰胺)苯基)-5-(三氟甲基)-1H-吡唑-4-甲酸(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 免疫组织化学检查神经胶质细胞的积累。超急性和急性脑出血中星形胶质细胞丰富，但MMΦ很少。抑制星形胶质细胞活性后，ICH大鼠表现出血肿扩张面积减小、血脑屏障破坏减少、血肿周围星形胶质细胞积聚减少、血液溶解过程延迟并获得更好的结果。这些发现提供的证据表明，活化的星形胶质细胞是超急性和急性脑出血中的关键细胞群，它们的调节可能为新的治疗和患者管理提供机会。
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 (n = 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.
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影响因子：
9.9
作者：
MAYER, SA;SACCO, RL;MOHR, JP
通讯作者：
MOHR, JP
影响因子：
8.3
作者：
Gonzales, Nicole R.
通讯作者：
Gonzales, Nicole R.
影响因子：
8.3
作者：
Lord AS;Gilmore E;Choi HA;Mayer SA;VISTA-ICH Collaboration
通讯作者：
VISTA-ICH Collaboration
影响因子：
4.7
作者：
Laird MD;Sukumari-Ramesh S;Swift AE;Meiler SE;Vender JR;Dhandapani KM
通讯作者：
Dhandapani KM
影响因子：
2.5
作者：
Festing, MFW
通讯作者：
Festing, MFW