BACKGROUND AND PURPOSE: Our aim was to assess the spatiotemporal evolution of the cerebrovascular inflammation occurring after ischemic and hemorrhagic strokes using a recently developed, fast, and ultra-sensitive molecular MRI method. METHODS: We first assessed longitudinally the cerebrovascular inflammation triggered by collagenase-induced hemorrhage and by permanent/transient middle cerebral artery occlusion in mice, using MRI after injection of microparticles of iron oxide targeted to vascular cell adhesion molecule-1 (MPIOs-αVCAM-1). Thereafter, we used this method to study the anti-inflammatory effects of celecoxib, atorvastatin, and dipyridamole after stroke. RESULTS: Using multiparametric MRI, we demonstrated that the level and the kinetics of cerebrovascular VCAM-1 expression depend on several parameters, including stroke pathogenesis, the natural history of the disease, and the administration of inflammation-modulating drugs. Interestingly, in transient middle cerebral artery occlusion and intracranial hemorrhage models, VCAM-1 expression was maximal at 24 hours and almost returned to baseline 5 days after stroke onset. In contrast, after permanent middle cerebral artery occlusion, VCAM-1 overexpression was sustained between 24 hours and 5 days, and was particularly significant in the peri-infarct areas. Our results suggest that these perilesional areas expressing VCAM-1 constitute an inflammatory penumbra that is recruited by the ischemic core during the subacute phase. Using MPIOs-αVCAM-1-enhanced imaging, we also provided evidence that celecoxib and atorvastatin (but not dipyridamole) alleviate VCAM-1 overexpression after stroke and prevent formation of the inflammatory penumbra. CONCLUSIONS: MPIOs-αVCAM-1-enhanced imaging seems to be promising in the detection of individuals presenting with severe cerebrovascular responses after stroke, which could therefore benefit from anti-inflammatory treatments.
BACKGROUND AND PURPOSE: Our aim was to assess the spatiotemporal evolution of the cerebrovascular inflammation occurring after ischemic and hemorrhagic strokes using a recently developed, fast, and ultra-sensitive molecular MRI method. METHODS: We first assessed longitudinally the cerebrovascular inflammation triggered by collagenase-induced hemorrhage and by permanent/transient middle cerebral artery occlusion in mice, using MRI after injection of microparticles of iron oxide targeted to vascular cell adhesion molecule-1 (MPIOs-αVCAM-1). Thereafter, we used this method to study the anti-inflammatory effects of celecoxib, atorvastatin, and dipyridamole after stroke. RESULTS: Using multiparametric MRI, we demonstrated that the level and the kinetics of cerebrovascular VCAM-1 expression depend on several parameters, including stroke pathogenesis, the natural history of the disease, and the administration of inflammation-modulating drugs. Interestingly, in transient middle cerebral artery occlusion and intracranial hemorrhage models, VCAM-1 expression was maximal at 24 hours and almost returned to baseline 5 days after stroke onset. In contrast, after permanent middle cerebral artery occlusion, VCAM-1 overexpression was sustained between 24 hours and 5 days, and was particularly significant in the peri-infarct areas. Our results suggest that these perilesional areas expressing VCAM-1 constitute an inflammatory penumbra that is recruited by the ischemic core during the subacute phase. Using MPIOs-αVCAM-1-enhanced imaging, we also provided evidence that celecoxib and atorvastatin (but not dipyridamole) alleviate VCAM-1 overexpression after stroke and prevent formation of the inflammatory penumbra. CONCLUSIONS: MPIOs-αVCAM-1-enhanced imaging seems to be promising in the detection of individuals presenting with severe cerebrovascular responses after stroke, which could therefore benefit from anti-inflammatory treatments.
Authors: Aurélien Quenault; Sara Martinez de Lizarrondo; Olivier Etard; Maxime Gauberti; Cyrille Orset; Benoît Haelewyn; Helen C Segal; Peter M Rothwell; Denis Vivien; Emmanuel Touzé; Carine Ali Journal: Brain Date: 2016-11-08 Impact factor: 13.501
Authors: Dominic A Siler; Yosef A Berlow; Ayaka Kukino; Catherine M Davis; Jonathan W Nelson; Marjorie R Grafe; Hirohisa Ono; Justin S Cetas; Martin Pike; Nabil J Alkayed Journal: Stroke Date: 2015-05-19 Impact factor: 7.914
Authors: Oscar A Marcos-Contreras; Colin F Greineder; Raisa Yu Kiseleva; Hamideh Parhiz; Landis R Walsh; Viviana Zuluaga-Ramirez; Jacob W Myerson; Elizabeth D Hood; Carlos H Villa; Istvan Tombacz; Norbert Pardi; Alecia Seliga; Barbara L Mui; Ying K Tam; Patrick M Glassman; Vladimir V Shuvaev; Jia Nong; Jacob S Brenner; Makan Khoshnejad; Tom Madden; Drew Weissmann; Yuri Persidsky; Vladimir R Muzykantov Journal: Proc Natl Acad Sci U S A Date: 2020-01-31 Impact factor: 11.205
Authors: Sara Martinez de Lizarrondo; Clément Gakuba; Bradley A Herbig; Yohann Repessé; Carine Ali; Cécile V Denis; Peter J Lenting; Emmanuel Touzé; Scott L Diamond; Denis Vivien; Maxime Gauberti Journal: Circulation Date: 2017-05-09 Impact factor: 29.690