Neuroinflammation and Infection: Molecular Mechanisms Associated with Dysfunction of Neurovascular Unit

Neuroinflammation is a complex inflammatory process in the central nervous system, which is sought to play an important defensive role against various pathogens, toxins or factors that induce neurodegeneration. The onset of neurodegenerative diseases and various microbial infections are counted as stimuli that can challenge the host immune system and trigger the development of neuroinflammation. The homeostatic nature of neuroinflammation is essential to maintain the neuroplasticity. Neuroinflammation is regulated by the activity of neuronal, glial, and endothelial cells within the neurovascular unit, which serves as a “platform” for the coordinated action of pro- and anti-inflammatory mechanisms. Production of inflammatory mediators (cytokines, chemokines, reactive oxygen species) by brain resident cells or cells migrating from the peripheral blood, results in the impairment of blood-brain barrier integrity, thereby further affecting the course of local inflammation. In this review, we analyzed the most recent data on the central nervous system inflammation and focused on major mechanisms of neurovascular unit dysfunction caused by neuroinflammation and infections

The first dinosaur egg from the Lower Cretaceous of Western Siberia, Russia

<p>The Lower Cretaceous Ilek Formation in Western Siberia (Russia) has yielded various vertebrate fossils, including skeletal remains of dinosaurs. Here we report on a fragmentary theropod egg from the vertebrate locality Shestakovo 3 of the Ilek Formation in Kemerovo Province. We assign the specimen to the oogenus <i>Prismatoolithus</i> (oofamily Prismatoolithidae) as <i>Prismatoolithus ilekensis</i> oosp. nov., on the basis of the following unique combination of characters: ovoid-shaped egg; thin eggshell 300–330 μm thick; angustiprismatic morphotype; eggshell with three different layers; gradual transition between mammillary layer and prismatic layer; abrupt contact between prismatic layer and external layer; mammillary layer to prismatic layer to external layer thickness ratio is 1:3:0.6; prismatic layer with ill-defined squamatic texture; angusticanaliculate pore system; and smooth outer surface. Like other Early Creataceous <i>Prismatoolithus</i>, the egg of <i>Prismatoolithus ilekensis</i> oosp. nov. was laid by a small bodied theropod dinosaur (troodontid or primitive bird) and this taxonomic attribution is supported by results of our phylogenetic analysis. <i>Prismatoolithus ilekensis</i> oosp. nov. is the first Early Cretaceous ootaxon from Russia.</p> <p>urn:lsid:zoobank.org:act:734EAD40-86C3-488B-A61E-B5FF7378BC0E</p

The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro

Abstract Background Lipopolysaccharide (LPS) is one of the main constituents of the cell wall of gram-negative bacteria. As an endotoxin, LPS induces neuroinflammation, which is associated with the blood-brain barrier impairment. Lactate is a metabolite with some significant physiological functions within the neurovascular unit/blood-brain barrier (BBB). Accumulation of extracellular and cerebrospinal fluid lactate is a specific feature of bacterial meningitis. However, the role of lactate production, transport, and sensing by lactate receptors GPR81 in the pathogenesis of bacterial neuroinflammation is still unknown. Methods In this study, we analyzed effects of LPS on the expression of GPR81 and MCT-1 and proliferation of cerebral endothelial cells in the BBB model in vitro. We used molecular profiling methods to measure the expression of GPR81, MCT-1, IL-1β, and Ki67 in the cerebral endothelium after treatment with different concentrations of LPS followed by measuring the level of extracellular lactate, transendothelial electric resistance, and permeability of the endothelial cell layer. Results Our findings showed that exposure to LPS results in neuroinflammatory changes associated with decreased expression of GPR81 and MCT-1 in endothelial cells, as well as overproduction of IL-1β and elevation of lactate concentrations in the extracellular space in a dose-dependent manner. LPS treatment reduced JAM tight junction protein expression in cerebral endothelial cells and altered BBB structural integrity in vitro. Conclusion The impairment of lactate reception and transport might contribute to the alterations of BBB structural and functional integrity caused by LPS-mediated neuroinflammation