Blood tissue Plasminogen Activator (tPA) of liver origin contributes to neurovascular coupling involving brain endothelial N-Methyl-D-Aspartate (NMDA) receptors.

Autor: Furon J; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France., Yetim M; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France., Pouettre E; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France., Martinez de Lizarrondo S; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France., Maubert E; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France., Hommet Y; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France., Lebouvier L; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France., Zheng Z; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.; Blood Research Institute, Versiti Blood Center of Wisconsin, Milwaukee, WI, USA., Ali C; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France., Vivien D; UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), Normandie University, Bvd Becquerel, BP 5229, 14074, Caen, France. vivien@cyceron.fr.; Department of Clinical Research, Caen-Normandie University Hospital, Caen, France. vivien@cyceron.fr.
Jazyk: angličtina
Zdroj: Fluids and barriers of the CNS [Fluids Barriers CNS] 2023 Feb 03; Vol. 20 (1), pp. 11. Date of Electronic Publication: 2023 Feb 03.
DOI: 10.1186/s12987-023-00411-w
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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