Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke
Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke
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DOI：
10.1093/brain/awm306
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发表时间：
2008-03-01
期刊：
影响因子：
14.5
通讯作者：
Roh, Jae-Kyu
中科院分区：
文献类型：
--
作者：
Lee, Soon-Tae;Chu, Kon;Roh, Jae-Kyu
神经干细胞（NSC）移植已被研究作为一种手段，以重建脑卒中后受损的大脑。然而，在这项研究中，我们研究了脑出血（ICH）后对急性脑和外周炎症的影响。在胶原酶诱导的大鼠模型ICH后2或24 h，静脉内（NSC-iv，500万个细胞）或脑内（NSC-ic，100万个细胞）注射来自胎儿人脑的NSC（HI克隆）。与注射载体的对照动物相比，只有NSC-iv-2 h导致较少的初始神经系统恶化和减少的脑水肿形成、炎性浸润（OX-42，髓过氧化物酶）和细胞凋亡（活化的半胱天冬酶-3，TUNEL）。大鼠神经球-iv-2 h，而不是人成纤维细胞-iv-2 h，也减少了脑水肿和最初的神经功能缺损。人NSC-iv-2 h还减弱了肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和核因子-κ B（NF-κ B）的脑和脾活化。然而，我们观察到只有少数干细胞在脑切片的神经干细胞-iv-2小时组;在主要的，他们被检测到边缘区的脾脏。为了研究NSC是否与脾脏相互作用以减少脑炎症，我们在ICH诱导之前进行了脾切除术，其消除了NSC-iv-2 h移植对脑含水量和炎性浸润的影响。神经干细胞也抑制在体外巨噬细胞激活后，脂多糖刺激的细胞与细胞接触依赖性的方式。总之，早期静脉注射NSC显示出抗炎功能，促进神经保护，主要是通过中断ICH后的脾脏炎症反应。
Neural stem cell (NSC) transplantation has been investigated as a means to reconstitute the damaged brain after stroke. In this study, however, we investigated the effect on acute cerebral and peripheral inflammation after intracerebral haemorrhage (ICH). NSCs (HI clone) from fetal human brain were injected intravenously (NSCs-iv, 5 million cells) or intracerebrally (NSCs-ic, 1 million cells) at 2 or 24 h after collagenase-induced ICH in a rat model. Only NSCs-iv-2 h resulted in fewer initial neurologic deteriorations and reduced brain oedema formation, inflammatory infiltrations (OX-42, myeloperoxidase) and apoptosis (activated caspase-3, TUNEL) compared to the vehicle-injected control animals. Rat neurosphere-iv-2 h, but not human fibroblast-iv-2 h, also reduced the brain oedema and the initial neurologic deficits. Human NSCs-iv-2 h also attenuated both cerebral and splenic activations of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-kappa B). However, we observed only a few stem cells in brain sections of the NSCs-iv-2 h group; in the main, they were detected in marginal zone of spleens. To investigate whether NSCs interact with spleen to reduce cerebral inflammation, we performed a splenectomy prior to ICH induction, which eliminated the effect of NSCs-iv-2 h transplantation on brain water content and inflammatory infiltrations. NSCs also inhibited in vitro macrophage activations after lipopolysaccharide stimulation in a cell-to-cell contact dependent manner. In summary, early intravenous NSC injection displayed anti-inflammatory functionality that promoted neuroprotection, mainly by interrupting splenic inflammatory responses after ICH.