scholarly journals Longitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
William Schreiber-Stainthorp ◽  
Jeffrey Solomon ◽  
Ji Hyun Lee ◽  
Marcelo Castro ◽  
Swati Shah ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Contrast Material ◽  
Blood Brain Barrier Disruption ◽  
Monkey Model ◽  
Quantitative Mr ◽  
Vaccine Treatment ◽  
Cytokine Levels ◽  
The Central Nervous System ◽  
Brain Barrier Disruption

AbstractEbola virus (EBOV) causes neurological symptoms yet its effects on the central nervous system (CNS) are not well-described. Here, we longitudinally assess the acute effects of EBOV on the brain, using quantitative MR-relaxometry, 18F-Fluorodeoxyglucose PET and immunohistochemistry in a monkey model. We report blood–brain barrier disruption, likely related to high cytokine levels and endothelial viral infection, with extravasation of fluid, Gadolinium-based contrast material and albumin into the extracellular space. Increased glucose metabolism is also present compared to the baseline, especially in the deep gray matter and brainstem. This regional hypermetabolism corresponds with mild neuroinflammation, sporadic neuronal infection and apoptosis, as well as increased GLUT3 expression, consistent with increased neuronal metabolic demands. Neuroimaging changes are associated with markers of disease progression including viral load and cytokine/chemokine levels. Our results provide insight into the pathophysiology of CNS involvement with EBOV and may help assess vaccine/treatment efficacy in real time.

scholarly journals Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyao Peng ◽  
Zhixuan Luo ◽  
Shuang He ◽  
Luhua Zhang ◽  
Ying Li
Keyword(s):  
Blood Brain Barrier ◽  
Barrier Function ◽  
Vascular System ◽  
Brain Barrier ◽  
Inflammatory Factors ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Brain Barrier Disruption ◽  
The Relationship

As a complex multicellular structure of the vascular system at the central nervous system (CNS), the blood-brain barrier (BBB) separates the CNS from the system circulation and regulates the influx and efflux of substances to maintain the steady-state environment of the CNS. Lipopolysaccharide (LPS), the cell wall component of Gram-negative bacteria, can damage the barrier function of BBB and further promote the occurrence and development of sepsis-associated encephalopathy (SAE). Here, we conduct a literature review of the direct and indirect damage mechanisms of LPS to BBB and the relationship between these processes and SAE. We believe that after LPS destroys BBB, a large number of inflammatory factors and neurotoxins will enter and damage the brain tissue, which will activate brain immune cells to mediate inflammatory response and in turn further destroys BBB. This vicious circle will ultimately lead to the progression of SAE. Finally, we present a succinct overview of the treatment of SAE by restoring the BBB barrier function and summarize novel opportunities in controlling the progression of SAE by targeting the BBB.

scholarly journals Feridex Preloading Permits Tracking of CNS-Resident Macrophages after Transient Middle Cerebral Artery Occlusion

2009 ◽  
Vol 29 (7) ◽  
pp. 1229-1239 ◽  
Author(s):  
Erica C Henning ◽  
Christi A Ruetzler ◽  
Martin R Gaudinski ◽  
Tom C-C Hu ◽  
Lawrence L Latour ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Artery Occlusion ◽  
Iron Oxide Particles ◽  
Spontaneously Hypertensive ◽  
Inflammatory Cascade ◽  
Blood Brain Barrier Disruption ◽  
Integral Role ◽  
The Central Nervous System ◽  
Brain Barrier Disruption ◽  
Magnetic Resonance Imaging Mri

At this time, the pathophysiology of macrophage involvement and their role in stroke progression are poorly understood. Recently, T2- and T2*-weighted magnetic resonance imaging (MRI), after intravenous administration of iron-oxide particles, have been used to understand the inflammatory cascade. Earlier studies report that image enhancement after stroke is from iron-laden macrophages; however, they do not account for potential blood-brain barrier disruption and nonspecific contrast enhancement. In this study, spontaneously hypertensive rats were preloaded with Feridex 7 days before stroke, permitting the labeling of bone-marrow-derived macrophages. Three-dimensional gradient-echo imaging showed average signal decreases of 13% to 23% in preloaded animals, concentrated on the lesion periphery and reaching a maximum on days 2 to 4 after stroke. Immunohistochemistry showed ED-2+, PB+, MHC-II+ and TNF-α+ perivascular macrophages (PVM), meningeal macrophages (MM), and choroid plexus macrophages (CPM). ED-1+ and IBA+ tissue macrophages and/or activated microglia were located throughout the lesion, but were PB−. These findings indicate the following: (1) Feridex preloading permits tracking of the central nervous system (CNS)-resident macrophages (PVM, MM, and CPM) and (2) CNS-resident macrophages likely play an integral role in the inflammatory cascade through antigen presentation and expression of proinflammatory cytokines. Further refinement of this method should permit noninvasive monitoring of inflammation and potential evaluation of antiinflammatory therapies in preclinical models of stroke.

scholarly journals Rapid, Nitric Oxide Synthesis-Dependent Activation of MMP-9 at Pericyte Somata During Capillary Ischemia in vivo

2021 ◽  
Vol 11 ◽  
Author(s):  
Robert G. Underly ◽  
Andy Y. Shih
Keyword(s):  
Nitric Oxide ◽  
Protein Synthesis ◽  
Vascular Pathology ◽  
Blood Brain Barrier Disruption ◽  
Vascular Physiology ◽  
Brain Barrier Disruption ◽  
Inhibitor Of Protein Synthesis ◽  
Oxide Synthase ◽  
Nos Isoforms

Nitric oxide serves essential roles in normal vascular physiology, but paradoxically contributes to vascular pathology in disease. During brain ischemia, aberrant nitric oxide levels can cause cellular injury through induction of nitrosative/oxidative stress and post-translational activation of matrix-metalloproteinase-9 (MMP-9). We recently demonstrated that brain pericyte somata were associated with very early and localized MMP-9 activation along capillaries during cerebral ischemia, leading to focal blood-brain barrier disruption. Here, we tested whether this effect was dependent upon nitric oxide production. In vivo two-photon imaging was used to directly visualize MMP9 activity using a FITC-gelatin probe and leakage of intravenous dye during photothrombotically induced capillary ischemia. Results showed that the NOS inhibitor, L-NIL, at concentrations affecting both iNOS and constitutive NOS isoforms, attenuated capillary leakage at pericyte soma-specific locations and substantially reduced FITC-gelatin cleavage. We also found that combined administration of L-NIL and anisomycin, an inhibitor of protein synthesis, led to near complete elimination of FITC-gelatin cleavage and vascular leakage. These results indicate that both nitric oxide synthase and new protein synthesis are involved in the rapid activation of MMP-9 at somata of capillary pericytes during ischemia.

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