Microbial Induction of Vascular Pathology in the CNS

Abstract

The central nervous system (CNS) is a finely tuned organ that participates in nearly every aspect of our day-to-day function. Neurons lie at the core of this functional unit and maintain an active dialogue with one another as well as their fellow CNS residents (e.g. astrocytes, oligodendrocytes, microglia). Because of this complex dialogue, it is essential that the CNS milieu be tightly regulated in order to permit uninterrupted and efficient neural chemistry. This is accomplished in part by anatomical barriers that segregate vascular components from the cerebral spinal fluid (CSF) and brain parenchyma. These barriers impede entry of noxious materials and enable the CNS to maintain requisite protein and ionic balances for constant electrochemical signaling. Under homeostatic conditions, the CNS is protected by the presence of specialized endothelium/epithelium, the blood brain barrier (BBB), and the blood-CSF barrier. However, following CNS infection these protective barriers can be comprised, sometimes resulting in severe neurological complications triggered by an imbalance or blockage of neural chemistry. In some instances, these disruptions are severe enough to be fatal. This review focuses on a selection of microbes (both viruses and parasites) that compromise vascular barriers and induce neurological complications upon gaining access to the CNS. Emphasis is placed on CNS diseases that result from a pathogenic interplay between host immune defenses and the invading microbe.

STAT3 Regulates MMP3 in Heme-Induced Endothelial Cell Apoptosis

“…The sequestration of pRBCs in brain microcirculation in CM is due to the erythrocyte membrane protein 1 (pfEMP-1) expressed on pRBCs which adhere to endothelium through endothelial surface receptors [37], mainly ICAM-1 and CD36. The heterogeneity of the vascular endothelium in various locations in the body, characterized by the difference in expression levels of CD36 or ICAM-1 may play an important role in determining the type and severity of malaria.…”

Viral disruption of the blood–brain barrier

“…Some strains of Theiler’s murine encephalomyelitis virus, a positive-sense RNA virus, induce acute encephalitis with alterations in tight junction protein expression [68,69]. In meningitis caused by LCMV, a negative-sense RNA virus, virus-specific CD8 + T cells are required for induction of disease; they are recruited into the CNS, resulting in increased vascular permeability and BBB disruption [68]. However, uncal herniation due to ventricular leakage and edema, rather than the BBB damage, appear to be the cause of the fatal choriomeningitis [68,70].…”

Illuminating viral infections in the nervous system

“…Intravital TPLSM has been used to monitor the pathogenic activities of green fluorescent protein (GFP)-tagged LCMV-specific CTLs through a thinned skull window 104,108 (FIGS 3,4; Supplementary information S4,S5 (movies)). In symptomatic mice (at day 6 post infection), an abundance of virus-specific CTLs were found actively scanning the infected meninges; however, no visual evidence directly linked these CTLs to vascular pathology.…”