Physiological Pathways Responsible for the Breakdown of the Blood Brain Barrier during Viral Encephalitis
During experimental viral encephalitis, mice infected with vesicular stomatitis virus (VSV) develop both innate and acquired immune responses to the infection. Many mice are spontaneously able to efficiently activate these host responses and limit viral replication, leading to survival. Other individuals develop pathologies including infection of a central regulatory region of the CNS, the locus ceruleus,infection of the lumbar sacral spinal cord (leading to hind-limb paralysis), or develop dysregulation of the blood brain barrier (BBB). These pathologies are frequently associated with a lethal outcome from infection. While we have studied many aspects of the hosts’ response to VSV infection including the effects of exogenous cytokine treatment, the role of IFN-γ and the inflammatory cells as well as the signals which have recruited them to the infection, this article will be restricted to the factors we have observed to regulate the integrity of the BBB during experimental VSV encephalitis. These mediators include nitric oxide and eicosinoids Prostaglandins and leukotrienes. By understanding the underlying physiology of the breakdown of the BBB, future treatments will be developed and applied to humans who have viral or bacterial infections of the CNS.
KeywordsNitric Oxide Vascular Endothelial Growth Factor Blood Brain Barrier Olfactory Bulb Evans Blue
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