Poly-ICLC preconditioning protects the blood-brain barrier against ischemic injury in vitro through type i interferon signaling

Raffaella Gesuete, Amy E B Packard, Keri B. Vartanian, Valerie K. Conrad, Susan L. Stevens, Frances Bahjat, Tao Yang, Mary Stenzel-Poore

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)75-85
Number of pages11
JournalJournal of Neurochemistry
Volume123
Issue numberSUPPL. 2
DOIs
StatePublished - Nov 2012

Fingerprint

Blood-Brain Barrier
Interferons
Wounds and Injuries
Brain
Interferon Type I
Stroke
Theoretical Models
Transcytosis
Poly I-C
poly ICLC
In Vitro Techniques
Endothelial cells
Microglia
Electric Impedance
Astrocytes
Brain Injuries
Neurons
Endothelium
Ischemia
Endothelial Cells

Keywords

  • blood-brain barrier
  • interferon-β
  • ischemia
  • preconditioning
  • stroke

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Poly-ICLC preconditioning protects the blood-brain barrier against ischemic injury in vitro through type i interferon signaling. / Gesuete, Raffaella; Packard, Amy E B; Vartanian, Keri B.; Conrad, Valerie K.; Stevens, Susan L.; Bahjat, Frances; Yang, Tao; Stenzel-Poore, Mary.

In: Journal of Neurochemistry, Vol. 123, No. SUPPL. 2, 11.2012, p. 75-85.

Research output: Contribution to journalArticle

Gesuete, Raffaella ; Packard, Amy E B ; Vartanian, Keri B. ; Conrad, Valerie K. ; Stevens, Susan L. ; Bahjat, Frances ; Yang, Tao ; Stenzel-Poore, Mary. / Poly-ICLC preconditioning protects the blood-brain barrier against ischemic injury in vitro through type i interferon signaling. In: Journal of Neurochemistry. 2012 ; Vol. 123, No. SUPPL. 2. pp. 75-85.
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