Activation of G protein-coupled estrogen receptor 1 (GPER-1) ameliorates blood-brain barrier permeability after global cerebral ischemia in ovariectomized rats.
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.
Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Dan
D
Lu
Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Yan
Y
Qu
Department of Aerospace Biodynamics, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Fei
F
Shi
Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Dayun
D
Feng
Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Kai
K
Tao
Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Guodong
G
Gao
Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Shiming
S
He
Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: zhaotianzhi1981@163.com.
Tianzhi
T
Zhao
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002199:Capillary Permeability; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C520305:Gper1 protein, rat; D007074:Immunoglobulin G; D018696:Neuroprotective Agents; D043562:Receptors, G-Protein-Coupled; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
Blood-brain barrier; G protein-coupled estrogen receptor 1; Ischemic stroke; Tight junction; Vascular endothelial growth factor A