Faculty Collaboration Database

Blood tissue Plasminogen Activator (tPA) of liver origin contributes to neurovascular coupling involving brain endothelial N-Methyl-D-Aspartate (NMDA) receptors. Fluids Barriers CNS 2023 Feb 03;20(1):11

Date

02/05/2023

Pubmed ID

36737775

Pubmed Central ID

PMC9896721

DOI

10.1186/s12987-023-00411-w

Scopus ID

2-s2.0-85147445875 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

BACKGROUND: Regulation of cerebral blood flow (CBF) directly influence brain functions and dysfunctions and involves complex mechanisms, including neurovascular coupling (NVC). It was suggested that the serine protease tissue-type plasminogen activator (tPA) could control CNV induced by whisker stimulation in rodents, through its action on N-methyl-D-Aspartate receptors (NMDARs). However, the origin of tPA and the location and mechanism of its action on NMDARs in relation to CNV remained debated.

METHODS: Here, we answered these issues using tPA^Null mice, conditional deletions of either endothelial tPA (VECad-Cre^ΔtPA) or endothelial GluN1 subunit of NMDARs (VECad-Cre^ΔGluN1), parabioses between wild-type and tPA^Null mice, hydrodynamic transfection-induced deletion of liver tPA, hepatectomy and pharmacological approaches.

RESULTS: We thus demonstrate that physiological concentrations of vascular tPA, achieved by the bradykinin type 2 receptors-dependent production and release of tPA from liver endothelial cells, promote NVC, through a mechanism dependent on brain endothelial NMDARs.

CONCLUSIONS: These data highlight a new mechanism of regulation of NVC involving both endothelial tPA and NMDARs.

Author List

Furon J, Yetim M, Pouettre E, Martinez de Lizarrondo S, Maubert E, Hommet Y, Lebouvier L, Zheng Z, Ali C, Vivien D

Author

Ze Zheng PhD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Brain
Endothelial Cells
Liver
Mice
Mice, Knockout
N-Methylaspartate
Neurovascular Coupling
Receptors, N-Methyl-D-Aspartate
Tissue Plasminogen Activator