Gamma Interferon Alters Junctional Integrity via Rho Kinase, Resulting in Blood-Brain Barrier Leakage in Experimental Viral Encephalitis
Abstract
Blood-brain barrier (BBB) breakdown is a hallmark of many diseases of the central nervous system (CNS). Loss of BBB integrity in CNS diseases such as viral encephalitis results in the loss of nutrient/oxygen delivery, rapid infiltration of immune cells, and brain swelling that can exacerbate neuronal injury. Despite this, the cellular and molecular mechanisms that underlie BBB breakdown in viral encephalitis are incompletely understood. We undertook a comprehensive analysis of the cellular and molecular signaling events that induce BBB breakdown in an experimental model of virus-induced encephalitis in which neonatal mice are infected with reovirus (serotype 3 strain Abney). We show that BBB leakage during reovirus infection correlates with morphological changes in the vasculature, reductions in pericytes (BBB supporting cells), and disorganization of vascular junctions. Pathway analysis on RNA sequencing from brain endothelial cells identified the activation of interferon (IFN) signaling within the brain vasculature following reovirus infection. Our in vitro and in vivo studies show that type II IFN mediated by IFN-γ, a well known antiviral signal, is a major contributor to BBB leakage during reovirus infection. We show that I...Continue Reading
References
Citations
West Nile Virus-Induced Neurologic Sequelae-Relationship to Neurodegenerative Cascades and Dementias
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Blood Brain Barrier
The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.
Blood Brain Barrier Regulation in Health & Disease
The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.
Blood Brain Barrier Chips
The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.
Blood Brain Barrier & Cytokines
Some cytokines are able to cross the blood brain barrier through transport systems and enter the cerebrospinal fluid and interstitial fluid spaces. Here is the latest research on cytokines crossing the blood brain barrier and how this can affect tissues within the CNS.