title: Malvidin's Effects on Rat Pial Microvascular Permeability Changes Due to Hypoperfusion and Reperfusion Injury.
abstract: The present study was aimed to evaluate the malvidin's protective effects on damage induced by 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion (RE) in rat pial microcirculation. Rat pial microcirculation was observed using fluorescence microscopy through a closed cranial window. Western blotting analysis was performed to investigate the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) and matrix metalloproteinase 9 (MMP-9) expression. Moreover, MMP-9 activity was evaluated by zymography. Finally, neuronal damage and radical oxygen species (ROS) formation were assessed. In all animals, pial arterioles were classified in five orders of branching according to Strahler's method. In hypoperfused rats, 30 min BCCAO and 60 min RE caused a decrease in arteriolar diameter, an increase in microvascular leakage and leukocyte adhesion, accompanied by decreased capillary perfusion and red blood cell velocity (VRBC). Moreover, marked neuronal damage and evident ROS generation were detected. Conversely, malvidin administration induced arteriolar dilation in dose-related manner, reducing microvascular leakage as well as leukocyte adhesion. Capillary perfusion and VRBC were protected. Nitric oxide (NO) synthase inhibition significantly attenuated malvidin's effects on arteriolar diameter. Western blotting analysis revealed an increase in eNOS and p-eNOS expression, while zymography indicated a decrease in MMP-9 activity after malvidin's administration. Furthermore, malvidin was able to prevent neuronal damage and to decrease ROS generation. In conclusion, malvidin protects rat pial microcirculation against BCCAO/RE injury, preventing blood-brain impairment and neuronal loss. Malvidin's effects appear to be mediated by eNOS activation and scavenger activity.
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Dominga
authors.initials: D
authors.lastname: Lapi
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Chiurazzi
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Di Maro
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mastantuono
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Battiloro
authors.affiliation: Department of Science and Technology, University of Sannio Benevento, Italy.
authors.forename: Lina
authors.initials: L
authors.lastname: Sabatino
authors.affiliation: Department of Translational Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ricci
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Rome, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: Di Carlo
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Noemy
authors.initials: N
authors.lastname: Starita
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Guida
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Santillo
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Colantuoni
keywords: bilateral common carotid artery occlusion; endothelial nitric oxide synthase; malvidin; metalloproteinases; pial microcirculation; radical oxygen species; reperfusion; zymography