期刊
EXPERIMENTAL NEUROLOGY
卷 207, 期 2, 页码 186-194出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2007.06.028
关键词
stroke; TNF alpha; leukocytes; chemotaxis
资金
- NCI NIH HHS [CA114197, R01 CA114197-03, R01 CA114197] Funding Source: Medline
- NEI NIH HHS [R01 EY014576-03] Funding Source: Medline
- NHLBI NIH HHS [HL66360, R01 HL066360-04] Funding Source: Medline
- NICHD NIH HHS [P30 HD015052, P30HD15052] Funding Source: Medline
- NIGMS NIH HHS [R01 GM070967-02] Funding Source: Medline
- NINDS NIH HHS [NS50396, NS21045, R37 NS021045, R01 NS050396, R01 NS050396-04] Funding Source: Medline
Cerebrovascular inflammation contributes to secondary brain injury following ischemia. Recent in vitro studies of cell migration and molecular guidance mechanisms have indicated that the Slit family of secreted proteins can exert repellant effects on leukocyte recruitment in response to chemoattractants. Utilizing intravital microscopy, we addressed the role of Slit in modulating leukocyte dynamics in the mouse cortical venular microcirculation in vivo following TNF alpha application or global cerebral ischemia. We also studied whether Slit affected neuronal survival in the mouse global ischemia model as well as in mixed neuronal-glial cultures subjected to oxygen-glucose deprivation. We found that systemically administered Slit significantly attenuated cerebral microvessel leukocyte-endothelial adherence occurring 4 h after TNF alpha and 24 h after global cerebral ischemia. Administration of RoboN, the soluble receptor for Slit, exacerbated the acute chemotactic response to TNFa. These findings are indicative of a tonic repellant effect of endogenous Slit in brain under acute proinflammatory conditions. Three days of continuous systemic administration of Slit following global ischemia significantly attenuated the delayed neuronal death of hippocampal CAI pyramidal cells. Moreover, Slit abrogated neuronal death in mixed neuronal-glial cultures exposed to oxygen-glucose deprivation. The ability of Slit to reduce the recruitment of immune cells to ischemic brain and to provide cytoprotective effects suggests that this protein may serve as a novel antiinflammatory and neuroprotective target for stroke therapy. Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据