Glial Cells Drive Preconditioning-Induced Blood-Brain Barrier Protection
| Autor: | Mária A. Deli, Diego Albani, Raffaella Gesuete, Elisa R. Zanier, Franca Orsini, Gianfranco Bazzoni, Maria Grazia De Simoni |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Ischemia Nerve Tissue Proteins Blood–brain barrier Brain Ischemia Mice chemistry.chemical_compound Glial Fibrillary Acidic Protein medicine Animals Claudin-5 Ischemic Preconditioning Microvessel Barrier function Evans Blue Advanced and Specialized Nursing Glial fibrillary acidic protein biology business.industry Membrane Proteins Infarction Middle Cerebral Artery Phosphoproteins medicine.disease Coculture Techniques Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure chemistry Blood-Brain Barrier Astrocytes Zonula Occludens-1 Protein biology.protein Ischemic preconditioning Endothelium Vascular Neurology (clinical) Cardiology and Cardiovascular Medicine business Neuroglia Astrocyte |
| Zdroj: | Stroke. 42:1445-1453 |
| ISSN: | 1524-4628 0039-2499 |
| DOI: | 10.1161/strokeaha.110.603266 |
| Popis: | Background and Purpose— The cerebrovascular contribution to ischemic preconditioning (IPC) has been scarcely explored. Using in vivo and in vitro approaches, we investigated the involvement of the blood-brain barrier and the role of its cellular components. Methods— Seven-minute occlusion of the right middle cerebral artery, used as in vivo IPC stimulus 4 days before permanent occlusion of the right middle cerebral artery, significantly reduced brain infarct size (8.45±0.7 versus 13.61±0.08 mm 3 measured 7 days after injury) and preserved blood-brain barrier function (Evans blue leakage, 0.54±0.1 versus 0.89±0.1 ng/mg). Assessment of neuronal, endothelial, and glial gene expression revealed that IPC specifically increased glial fibrillary acidic protein mRNA, thus showing selective astrocyte activation in IPC-protected mice. Results— The blood-brain barrier was modeled by coculturing murine primary brain microvessel endothelial and astroglial cells. One-hour oxygen-glucose deprivation (OGD), delivered 24 hours before a 5-hour OGD, acted as an IPC stimulus, significantly attenuating the reduction in transendothelial electric resistance (199.17±11.7 versus 97.72±3.4 Ωcm 2 ) and the increase in permeability coefficients for sodium fluorescein (0.98±0.11×10 −3 versus 1.8±0.36×10 −3 cm/min) and albumin (0.12±0.01×10 −3 versus 0.29±0.07×10 −3 cm/min) induced by severe OGD. IPC also prevented the 5-hour OGD–induced disorganization of the tight junction proteins ZO-1 and claudin-5. IPC on glial (but not endothelial) cells alone preserved transendothelial electric resistance, permeability coefficients, and ZO-1 localization after 5 hours of OGD. Astrocyte metabolic inhibition by fluorocitrate abolished IPC protection, confirming the critical role of astrocytes. IPC significantly increased glial fibrillary acidic protein, interleukin-6, vascular endothelial growth factor-a, and ciliary neurotrophic factor gene expression after OGD in glial cells, indicating that multiple pathways mediate the glial contribution to IPC. Conclusions— Our data show that the blood-brain barrier can be directly preconditioned and that astrocytes are major mediators of IPC protection. |
| Databáze: | OpenAIRE |
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