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

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 1h 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.

• Authors: Ebony Washington Remus, Iqbal Sayeed, Soonmi Won, Alicia N Lyle, Donald G Stein
• Journal: Experimental neurology (Exp Neurol) Vol. 271 Pg. 401-8 (Sep 2015) ISSN: 1090-2430 [Electronic] United States
• PMID: 26188381 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD68 antigen, human
• Ccl2 protein, rat
• Chemokine CCL2
• Chemokine CXCL1
• Cxcl1 protein, rat
• Cytokines
• Ki-67 Antigen
• Progestins
• Progesterone

Topics

• Animals
• Antigens, CD (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Cell Hypoxia (drug effects)
• Cell Movement (drug effects)
• Cells, Cultured
• Chemokine CCL2 (metabolism)
• Chemokine CXCL1 (metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Endothelial Cells (drug effects)
• Gene Expression Regulation (drug effects)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, pathology)
• Ki-67 Antigen (metabolism)
• Macrophages (drug effects)
• Male
• Progesterone (therapeutic use)
• Progestins (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion