Subarachnoid Hemorrhage Induces Gliosis and Increased Expression of the Pro-inflammatory Cytokine High Mobility Group Box 1 Protein.

Subarachnoid Hemorrhage Induces Gliosis and Increased Expression of the Pro-inflammatory Cytokine High Mobility Group Box 1 Protein.
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DOI:
10.1007/s12975-010-0052-2
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发表时间:
2011-03-01
影响因子:
6.9
通讯作者:
Wellman GC
Wellman GC
中科院分区:
医学1区
文献类型:
--
作者:
Murakami K;Koide M;Dumont TM;Russell SR;Tranmer BI;Wellman GC

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脑动脉瘤破裂后蛛网膜下腔出血(SAH)与高发病率和死亡率相关。存活的SAH患者经常遭受神经功能损害,但目前对蛛网膜下腔血液对脑实质的影响知之甚少。本研究的目的是使用兔SAH模型检查蛛网膜下腔血液对胶质细胞的影响。星形胶质细胞特异性蛋白胶质细胞酸性蛋白(GFAP)和S100 B在SAH模型兔脑干中表达上调,与反应性星形胶质细胞增生的发展一致。除了反应性星形胶质细胞增生,SAH动物脑中促炎细胞因子高迁移率族蛋白1(HMGB1)的胞质表达增加。我们发现,超过90%的细胞表达胞质HMGB1免疫染色阳性的小胶质细胞和巨噬细胞的特异性标记物Iba1。此外,Iba1阳性细胞的数量在对照组和SAH动物的脑中相似,表明这些细胞中的大多数可能是常驻小胶质细胞,而不是浸润性巨噬细胞。这些观察结果表明,SAH通过激活星形胶质细胞和小胶质细胞,触发促炎细胞因子HMGB1的上调来影响脑实质。
Subarachnoid hemorrhage (SAH) following cerebral aneurysm rupture is associated with high rates of morbidity and mortality. Surviving SAH patients often suffer from neurological impairment, yet little is currently known regarding the influence of subarachnoid blood on brain parenchyma. The objective of the present study was to examine the impact of subarachnoid blood on glial cells using a rabbit SAH model. The astrocyte-specific proteins, glial fibrillary acidic protein (GFAP) and S100B, were up-regulated in brainstem from SAH model rabbits, consistent with the development of reactive astrogliosis. In addition to reactive astrogliosis, cytosolic expression of the pro-inflammatory cytokine, high-mobility group box 1 protein (HMGB1) was increased in brain from SAH animals. We found that greater than 90% of cells expressing cytosolic HMGB1 immunostained positively for Iba1, a specific marker for microglia and macrophages. Further, the number of Iba1-positive cells was similar in brain from control and SAH animals, suggesting the majority of these cells were likely resident microglial cells rather than infiltrating macrophages. These observations demonstrate SAH impacts brain parenchyma by activating astrocytes and microglia, triggering up-regulation of the pro-inflammatory cytokine HMGB1.
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