Stroke-Induced Brain Parenchymal Injury Drives Blood–Brain Barrier Early Leakage Kinetics: A Combined in Vivo / in Vitro Study

Autor: Mélanie Kuntz, Rustem Uzbekov, Vincent Berezowski, Olivier Pétrault, Régis Bordet, Laurence Fenart, Roméo Cecchelli, Maud Pétrault, Caroline Mysiorek
Přispěvatelé: Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA)
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Pathology
medicine.medical_specialty
magnetic resonance imaging (MRI)
Endothelium
[SDV]Life Sciences [q-bio]
Vascular permeability
Biology
Blood–brain barrier
Lesion
Brain ischemia
Capillary Permeability
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
In vivo
medicine
Animals
Cells
Cultured

030304 developmental biology
Evans Blue
0303 health sciences
cell culture
Cell Death
Endothelial Cells
medicine.disease
Magnetic Resonance Imaging
Coculture Techniques
brain ischemia
reperfusion
Mice
Inbred C57BL

Oxygen
Stroke
Disease Models
Animal

Kinetics
medicine.anatomical_structure
Glucose
Neurology
chemistry
Blood-Brain Barrier
Neuroglia
Original Article
Neurology (clinical)
medicine.symptom
Cardiology and Cardiovascular Medicine
030217 neurology & neurosurgery
Zdroj: Journal of Cerebral Blood Flow and Metabolism
Journal of Cerebral Blood Flow and Metabolism, Nature Publishing Group, 2014, 34 (1), pp.95-107. ⟨10.1038/jcbfm.2013.169⟩
Journal of Cerebral Blood Flow & Metabolism; Vol 34
ISSN: 0271-678X
1559-7016
DOI: 10.1038/jcbfm.2013.169⟩
Popis: International audience; The disappointing clinical outcomes of neuroprotectants challenge the relevance of preclinical stroke models and data in defining early cerebrovascular events as potential therapeutic targets. The kinetics of blood–brain barrier (BBB) leakage after reperfusion and the link with parenchymal lesion remain debated. By using in vivo and in vitro approaches, we conducted a kinetic analysis of BBB dysfunction during early reperfusion. After 60 minutes of middle cerebral artery occlusion followed by reperfusion times up to 24 hours in mice, a non-invasive magnetic resonance imaging method, through an original sequence of diffusion-weighted imaging, determined brain water mobility in microvascular compartments (D*) apart from parenchymal compartments (apparent diffusion coefficient). An increase in D* found at 4 hours post reperfusion concurred with the onset of both Evans blue/Dextran extravasations and in vitro BBB opening under oxygen-glucose deprivation and reoxygenation (R). The BBB leakage coincided with an emerging cell death in brain tissue as well as in activated glial cells in vitro. The co-culture of BBB endothelial and glial cells evidenced a recovery of endothelium tightness when glial cells were absent or non-injured during R. Preserving the ischemic brain parenchymal cells within 4 hours of reperfusion may improve therapeutic strategies for cerebrovascular protection against stroke.
Databáze: OpenAIRE