PMID- 26188381
OWN - NLM
STAT- MEDLINE
DCOM- 20151222
LR  - 20201226
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 271
DP  - 2015 Sep
TI  - Progesterone protects endothelial cells after cerebrovascular occlusion by 
      decreasing MCP-1- and CXCL1-mediated macrophage infiltration.
PG  - 401-8
LID - S0014-4886(15)30043-1 [pii]
LID - 10.1016/j.expneurol.2015.07.010 [doi]
AB  - 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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Remus, Ebony Washington
AU  - Remus EW
AD  - Department of Emergency Medicine Brain Research Laboratory, Emory University, 
      Atlanta, GA, USA.
FAU - Sayeed, Iqbal
AU  - Sayeed I
AD  - Department of Emergency Medicine Brain Research Laboratory, Emory University, 
      Atlanta, GA, USA.
FAU - Won, Soonmi
AU  - Won S
AD  - Department of Emergency Medicine Brain Research Laboratory, Emory University, 
      Atlanta, GA, USA.
FAU - Lyle, Alicia N
AU  - Lyle AN
AD  - Department of Cardiology, Emory University Atlanta, GA, USA.
FAU - Stein, Donald G
AU  - Stein DG
AD  - Department of Emergency Medicine Brain Research Laboratory, Emory University, 
      Atlanta, GA, USA. Electronic address: dstei04@emory.edu.
LA  - eng
GR  - U01 NS062676/NS/NINDS NIH HHS/United States
GR  - NIH UO1 NS062676/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150717
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Cxcl1 protein, rat)
RN  - 0 (Cytokines)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Progestins)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Cell Hypoxia/drug effects
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Chemokine CXCL1/*metabolism
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Endothelial Cells/*drug effects
MH  - Gene Expression Regulation/drug effects
MH  - *Infarction, Middle Cerebral Artery/drug therapy/metabolism/pathology
MH  - Ki-67 Antigen/metabolism
MH  - Macrophages/drug effects
MH  - Male
MH  - Progesterone/*therapeutic use
MH  - Progestins/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion
PMC - PMC4586408
MID - NIHMS710752
OTO - NOTNLM
OT  - Brain ischemia
OT  - Cerebrovascular repair
OT  - Endothelial cells
OT  - Macrophage infiltration
OT  - Progesterone
COIS- The authors have no conflicts of interest concerning this research.
EDAT- 2015/07/21 06:00
MHDA- 2015/12/23 06:00
PMCR- 2016/09/01
CRDT- 2015/07/20 06:00
PHST- 2015/05/14 00:00 [received]
PHST- 2015/06/29 00:00 [revised]
PHST- 2015/07/13 00:00 [accepted]
PHST- 2015/07/20 06:00 [entrez]
PHST- 2015/07/21 06:00 [pubmed]
PHST- 2015/12/23 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - S0014-4886(15)30043-1 [pii]
AID - 10.1016/j.expneurol.2015.07.010 [doi]
PST - ppublish
SO  - Exp Neurol. 2015 Sep;271:401-8. doi: 10.1016/j.expneurol.2015.07.010. Epub 2015 
      Jul 17.