Activation of G protein-coupled estrogen receptor 1 (GPER-1) ameliorates blood-brain barrier permeability after global cerebral ischemia in ovariectomized rats

Biochem Biophys Res Commun. 2016 Aug 19;477(2):209-14. doi: 10.1016/j.bbrc.2016.06.044. Epub 2016 Jun 13.


G protein-coupled estrogen receptor 1 (GPER-1) plays important roles in estrogen-mediated neuroprotection. However, protective effects of GPER-1 on blood-brain barrier (BBB) after ischemic stroke have not been determined. The aim of present study was to determine whether GPER-1 activation ameliorates BBB permeability in ovariectomized rats with induced global cerebral ischemia (GCI). GCI was induced by 4-vessel occlusion for 20 min followed by 24 h reperfusion period. The GPER-1 agonist (G1) was bilaterally administered immediately upon reperfusion by intracerebroventricular (icv) injection. We found that the GPER-1 agonist could significantly decrease immunoglobulin G (IgG) extravasation and increase the levels of tight junctions (occludin and claudin-5) in the CA1 at 24 h of reperfusion after GCI. Further, protein levels of vascular endothelial growth factor A (VEGF-A) was significantly decreased in the ischemic CA1 by G1. Our results suggest that GPER-1 activation reduce tight junctions disruption via inhibition of VEGF-A expression after ischemic injury.

Keywords: Blood-brain barrier; G protein-coupled estrogen receptor 1; Ischemic stroke; Tight junction; Vascular endothelial growth factor A.

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Brain Ischemia / metabolism*
  • Capillary Permeability
  • Dose-Response Relationship, Drug
  • Female
  • Hippocampus / metabolism*
  • Immunoglobulin G / metabolism*
  • Neuroprotective Agents / administration & dosage*
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*


  • Gper1 protein, rat
  • Immunoglobulin G
  • Neuroprotective Agents
  • Receptors, G-Protein-Coupled
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat