About this item:

274 Views | 397 Downloads

Author Notes:

Address for Correspondence: Donald G Stein, Ph.D., Department of Emergency Medicine Brain Research Laboratory 1365B Clifton Rd NE, Suite 5100, Emory University, Atlanta, GA 30322, USA, Voice: 404 712 2540, Fax: 404 727 2388, dstei04@emory.edu.

The authors have no conflicts of interest concerning this research.

Subjects:

Research Funding:

This work was supported by NIH UO1 NS062676 to DGS and AHA SDG grant 11SDG5430002 to IS.

Partial funding for some of the assays used in this project was provided by BHR Pharma and the Marcus Foundation.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Brain ischemia
  • Cerebrovascular repair
  • Endothelial cells
  • Macrophage infiltration
  • Progesterone
  • CEREBRAL-ARTERY OCCLUSION
  • BLOOD-BRAIN-BARRIER
  • ISCHEMIC-STROKE
  • ISCHEMIA/REPERFUSION INJURY
  • MYOCARDIAL-INFARCTION
  • EXPRESSION
  • RATS
  • ANGIOGENESIS

Progesterone protects endothelial cells after cerebrovascular occlusion by decreasing MCP-1-and CXCL1-mediated macrophage infiltration

Tools:

Journal Title:

Experimental Neurology

Volume:

Volume 271

Publisher:

, Pages 401-408

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The neuroprotective effects of progesterone after ischemic stroke have been established, but the role of progesterone in promoting cerebrovascular repair remains under-explored. Male Sprague-Dawley rats underwent transient middle cerebral artery occlusion (tMCAO) for 90. min followed by reperfusion for 3. days. Progesterone (8. mg/kg/day) was administered intraperitoneally at 1. h after initial occlusion followed by subcutaneous injections at 6, 24 and 48. h post-occlusion. Rats were euthanized after 72. h and brain endothelial cell density and macrophage infiltration were evaluated within the cerebral cortex. We also assessed progesterone's ability to induce macrophage migration toward hypoxic/reoxygenated cultured endothelial cells. We found that progesterone treatment post-tMCAO protects ischemic endothelial cells from macrophage infiltration. We further demonstrate that infiltration of monocytes/macrophages can be induced by potent chemotactic factors such as monocyte chemoattractant protein-1 (MCP-1) and the chemokine ligand 1 (CXCL1), secreted by hypoxic/reoxygenated endothelial cells. Progesterone blunts secretion of MCP-1 and CXCL1 from endothelial cells after hypoxia/reoxygenation injury and decreases leukocyte infiltration. The treatment protects ischemic endothelial cells from macrophage infiltration and thus preserves vascularization after ischemic injury.

Copyright information:

© 2015 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote