Effects of transient loss of shear stress on blood-brain barrier endothelium: role of nitric oxide and IL-6
| Autor: | Luca Cucullo, Fiona Parkinson, Miranda Kapural, Mohammed Hossain, Ljiljana Krizanac-Bengez, Marc R. Mayberg, Damir Janigro |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Time Factors medicine.medical_treatment Vascular permeability Lactose Pharmacology Rats Sprague-Dawley chemistry.chemical_compound Electric Impedance Enzyme Inhibitors Hypoxia Cells Cultured General Neuroscience Brain medicine.anatomical_structure Cytokine NG-Nitroarginine Methyl Ester Blood-Brain Barrier Cytokines medicine.symptom Shear Strength Endothelium Ischemia Inflammation Blood–brain barrier Nitric Oxide Models Biological Antibodies Nitric oxide Capillary Permeability medicine Animals Molecular Biology business.industry Interleukin-6 Cerebrovascular disorder medicine.disease Coculture Techniques Rats Glucose chemistry Animals Newborn Astrocytes Reperfusion Neurology (clinical) Endothelium Vascular business Neuroscience Developmental Biology Interleukin-1 |
| Zdroj: | Brain research. 977(2) |
| ISSN: | 0006-8993 |
| Popis: | Loss of blood-brain barrier (BBB) function may contribute to post-ischemic cerebral injury by yet unknown mechanisms. Ischemia is associated with anoxia, aglycemia and loss of flow (i.e. shearing forces). We tested the hypothesis that loss of shear stress alone does not acutely affect BBB function due to a protective cascade of mechanisms involving cytokines and nitric oxide (NO). To determine the relative contribution of shear stress on BBB integrity we used a dynamic in vitro BBB model based on co-culture of rat brain microvascular endothelial cells (RBMEC) and astrocytes. Trans-endothelial electrical resistance (TEER), IL-6 release and NO levels were measured from the lumenal and ablumenal compartments throughout the experiment. Flow-exposed RBMEC were challenged with 1 h of normoxic-normoglycemic flow cessation (NNFC) followed by reperfusion for 2 to 24 h. NNFC caused a progressive drop in nitric oxide production during flow cessation followed by a time-dependent increase in ablumenal IL-6 associated with a prolonged NO increase during reperfusion. The nitric oxide synthetase (NOS) inhibitor L-NAME (10 microM) abrogated all effects of NNFC, including changes in NO and cytokine production. BBB permeability did not increase during or after NNFC/reperfusion, but was increased by treatment with L-NAME or when the effects of IL-6 were blocked. Flow adapted RBMEC and astrocytes respond to NNFC/reperfusion by overproduction of IL-6, possibly secondary to increased production of NO during the reperfusion. Maintenance of BBB function during and following NNFC appears to depend on intact NO signaling and IL-6 release. |
| Databáze: | OpenAIRE |
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