Abstract:
:As a dual-acting neurotransmitter, glycine plays critical roles in cerebral ischemia by activating both glycine receptors (GlyRs) and N-methyl-D-aspartate acid receptors (NMDARs). However, the involvement of glycine receptor alpha 2 (GlyRa2) in cerebral ischemia has not been explored. The objective of this study was to determine the mechanism of action of GlyRa2 in cerebrovascular remodeling. After induction of rat tMCAO, levels of the GLRA2 gene and GlyRa2 protein were examined using q-PCR, western blot, and immunohistochemical analyses. Blood-brain barrier permeability, and the presence of hemorrhage and arteriosclerosis were also analyzed. The underlying mechanism of vascular remodeling was examined using immunohistochemical and immunofluorescence analyses. Both the GLRA2 gene and GlyRa2 protein were altered sharply after stroke. GlyRa2 of vascular origin appears to play a protective role after glycine treatment for ischemia. Blockade of GlyRa2 by the addition of cyclothiazide was found to abolish previous improvements in cerebrovascular survival after glycine treatment for tMCAO in rats. GlyRa2-dependent neurovascular remodeling was found to be correlated with the vascular endothelial growth factor receptor 2 (VEGFR2) pathways. These results suggest that vascular-derived GlyRa2 protects against post-ischemic injury. Vascular protection via GlyRa2 is due to VEGFR2/pSTAT3 signaling.
journal_name
Am J Transl Resjournal_title
American journal of translational researchauthors
Chen Z,Wang X,Liao H,Sheng T,Chen P,Zhou H,Pan Y,Liu W,Yao Hsubject
Has Abstractpub_date
2020-10-15 00:00:00pages
6895-6907issue
10issn
1943-8141journal_volume
12pub_type
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