Poly-ICLC preconditioning protects the blood–brain barrier against ischemic injury in vitro through type I interferon signaling
Article first published online: 11 OCT 2012
© 2012 The Authors Journal of Neurochemistry © International Society for Neurochemistry
Journal of Neurochemistry
Special Issue: Novel Therapeutic Strategies and Targets for the Treatment of Stroke
Volume 123, Issue Supplement s2, pages 75–85, November 2012
How to Cite
J. Neurochem. (2012) 123 (Suppl. 2), 75–85.
- Issue published online: 11 OCT 2012
- Article first published online: 11 OCT 2012
- Manuscript Revised: 1 AUG 2012
- Manuscript Accepted: 1 AUG 2012
- Manuscript Received: 8 JUN 2012
- National Institute of Neurological Disorders and Stroke. Grant Numbers: NS050567, NS062381
- blood–brain barrier;
Preconditioning with a low dose of harmful stimulus prior to injury induces tolerance to a subsequent ischemic challenge resulting in neuroprotection against stroke. Experimental models of preconditioning primarily focus on neurons as the cellular target of cerebral protection, while less attention has been paid to the cerebrovascular compartment, whose role in the pathogenesis of ischemic brain injury is crucial. We have shown that preconditioning with polyinosinic polycytidylic acid (poly-ICLC) protects against cerebral ischemic damage. To delineate the mechanism of poly-ICLC protection, we investigated whether poly-ICLC preconditioning preserves the function of the blood–brain barrier (BBB) in response to ischemic injury. Using an in vitro BBB model, we found that poly-ICLC treatment prior to exposure to oxygen-glucose deprivation maintained the paracellular and transcellular transport across the endothelium and attenuated the drop in transendothelial electric resistance. We found that poly-ICLC treatment induced interferon (IFN) β mRNA expression in astrocytes and microglia and that type I IFN signaling in brain microvascular endothelial cells was required for protection. Importantly, this implicates a potential mechanism underlying neuroprotection in our in vivo experimental stroke model, where type I IFN signaling is required for poly-ICLC-induced neuroprotection against ischemic injury. In conclusion, we are the first to show that preconditioning with poly-ICLC attenuates ischemia-induced BBB dysfunction. This mechanism is likely an important feature of poly-ICLC-mediated neuroprotection and highlights the therapeutic potential of targeting BBB signaling pathways to protect the brain against stroke.