The role of the choroid plexus in neutrophil invasion after traumatic brain injury.

The role of the choroid plexus in neutrophil invasion after traumatic brain injury.
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DOI:
10.1038/jcbfm.2009.71
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发表时间:
2009-09
期刊:
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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其他
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创伤性脑损伤(TBI)经常导致神经炎症,其包括中性粒细胞的侵入。TBI后,中性粒细胞浸润脉络丛(CP),血-脑脊液(CSF)屏障(BCSFB)的一个部位,并在损伤附近的CSF空间中积聚,这些炎性细胞可能从此处迁移到脑实质。我们假设CP是中性粒细胞侵入受损脑的入口点。使用大鼠TBI的受控皮质撞击模型和BCSFB的体外模型,我们表明CP产生CXC趋化因子,如奎宁诱导的中性粒细胞趋化因子(CINC)-1或CXCL 1,CINC-2α或CXCL 3,和CINC-3或CXCL 2。这些趋化因子从脉络膜上皮顶部和基底外侧分泌,是中性粒细胞迁移穿过上皮屏障的先决条件。与这些发现相一致,我们还提供了电镜证据表明中性粒细胞浸润脉络膜基质,随后到达脉络膜上皮细胞之间的细胞间隙。这是第一次详细分析与中性粒细胞运输相关的BCSFB功能。我们的观察结果支持这一屏障在创伤后中性粒细胞侵袭中的作用。
Traumatic brain injury (TBI) frequently results in neuroinflammation, which includes the invasion of neutrophils. After TBI, neutrophils infiltrate the choroid plexus (CP), a site of the blood-cerebrospinal fluid (CSF) barrier (BCSFB), and accumulate in the CSF space near the injury, from where these inflammatory cells may migrate to brain parenchyma. We have hypothesized that the CP functions as an entry point for neutrophils to invade the injured brain. Using the controlled cortical impact model of TBI in rats and an in vitro model of the BCSFB, we show that the CP produces CXC chemokines, such as cytokine-induced neutrophil chemoattractant (CINC)-1 or CXCL1, CINC-2α or CXCL3, and CINC-3 or CXCL2. These chemokines are secreted both apically and basolaterally from choroidal epithelium, a prerequisite for neutrophil migration across epithelial barriers. Consistent with these findings, we also provide electron microscopic evidence that neutrophils infiltrate the choroidal stroma and subsequently reach the intercellular space between choroidal epithelial cells. This is the first detailed analysis of the BCSFB function related to neutrophil trafficking. Our observations support the role of this barrier in post-traumatic neutrophil invasion.
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