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Updated: May 10, 2026
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Published on: September 4, 2013
Ultra-sensitive molecular MRI of vascular cell adhesion molecule-1 reveals a dynamic inflammatory penumbra after
Maxime Gauberti1, Axel Montagne, Oscar A Marcos-Contreras
1Institut National de la Santé Et de la Recherche Médicale (INSERM) U919 Serine Protease and Pathophysiology of the Neurovascular Unit, University Caen Basse-Normandie, GIP Cyceron, Bd Becquerel, BP5229, Caen, France.
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.
Insights
This study reveals that cerebrovascular inflammation after stroke varies by stroke type and time. Certain anti-inflammatory drugs effectively reduce this inflammation and prevent an "inflammatory penumbra".
Area of Science:
- Neuroscience
- Radiology
- Immunology
Background:
- Cerebrovascular inflammation plays a critical role in stroke pathogenesis.
- Understanding the spatiotemporal dynamics of this inflammation is crucial for developing effective treatments.
Purpose of the Study:
- To assess the spatiotemporal evolution of cerebrovascular inflammation after ischemic and hemorrhagic strokes.
- To evaluate the anti-inflammatory effects of celecoxib, atorvastatin, and dipyridamole using a novel MRI method.
Main Methods:
- Utilized a fast, ultra-sensitive molecular MRI method with microparticles of iron oxide targeted to vascular cell adhesion molecule-1 (MPIOs-αVCAM-1).
- Assessed inflammation longitudinally in mouse models of intracerebral hemorrhage and middle cerebral artery occlusion (MCAO).
Main Results:
- VCAM-1 expression kinetics varied with stroke type (hemorrhagic, transient MCAO, permanent MCAO) and disease progression.
- Permanent MCAO showed sustained VCAM-1 overexpression in peri-infarct areas, forming an 'inflammatory penumbra'.
- Celecoxib and atorvastatin, but not dipyridamole, reduced VCAM-1 overexpression and prevented inflammatory penumbra formation.
Conclusions:
- MPIOs-αVCAM-1-enhanced MRI is a promising tool for detecting severe cerebrovascular responses post-stroke.
- This imaging technique can identify patients who may benefit from targeted anti-inflammatory therapies.
