Gamma Interferon Alters Junctional Integrity via Rho Kinase, Resulting in Blood-Brain Barrier Leakage in Experimental Viral Encephalitis

Abstract

In an experimental viral encephalitis mouse model in which mice are infected with reovirus, we show that IFN-γ induces blood-brain barrier leakage. We show that IFN-γ promotes Rho kinase activity, resulting in actin cytoskeletal contractions in the brain endothelium that lead to vascular junctional disorganization and cell-cell separations. These studies now provide insight into a previously unknown mechanism for how blood-brain barrier breakdown occurs in viral encephalitis and implicates IFN-γ-Rho kinase activity as major contributor to this phenomenon. By identifying this mechanism of blood-brain barrier breakdown, we now provide potential therapeutic targets in treating patients with viral causes of encephalitis with the hope of limiting damage to the central nervous system.