Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier

Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens

Early experiences affect adaptability and the propensity for psychosomatic problems

Early experiences, particularly a perturbed mother-infant relationship, have been recognized as important factors for the development of psychopathology in adult life. However, the neurobiological mechanisms involved still remain elusive. An experimental paradigm employed for such purposes is “neonatal handling”, in which the pups are separated from the mother for a short period of time (15 min daily for the first 22 days of life). This experience permanently alters hypothalamic pituitary-adrenal (HPA) function and the ability of the organism to cope with stressful stimuli. Since dysregulation of the HPA axis has been clearly documented as playing an important role in the etiopathogenesis of depression, we investigated and demonstrated that neonatal handling has sex-dependent effects on the susceptibility to express “depressive” behavior in different animal models of depression. These effects could be mediated by changes in serotonin metabolism, shown to be induced by this early experience. In an effort to elucidate the molecular mechanisms underlying these early experience-induced changes, we determined the effect of handling on the expression of neurotrophins, since these molecules play an important role in brain plasticity. Neonatal handling resulted in changes in neurotrophin levels in the hippocampus, the brain area that plays an important role in learning, memory and adaptation. (C) 2002 Elsevier Science B.V. All rights reserved

The effects of adrenalectomy and thermal stress on glutamic acid decarboxylase activity in different regions of the rat brain

Glutamic acid decarboxylase (GAD) enzyme activity was measured in synaptosomes prepared from the hypothalamus, the hippocampus, the striatum and the cerebral cortex of control, adrenalectomized and rat exposed to a thermal stress. Adrenalectomy caused a statistically significant decrease in the enzyme activity in the striatum, while it had no effect in the other three brain areas. On the other hand, exposure to the thermal stress resulted in a dramatic increase of GAD specific activity in all brain areas examined. This thermal stress-induced increase in enzyme activity was observed in both non-operated and adrenalectomized animals, which implies that it is not mediated by glucocorticoids. © 1991 Plenum Publishing Corporation

Expression of IGF-i and IGF-II genes in the adult rat Eye

We have investigated the transcription of IGF-I and IGF-II genes in the adult rat eye. Each eye was dissected into cornea, lens, sclera+choroid+pigment epithelium, and neural retina. Total cellular RNA was isolated from each of these tissues. Northern blot analysis using rat coding region cDNA probes revealed the presence of IGF-I and IGF-II specific transcripts in the retina and the sclera but not in the lens and cornea. Retina demonstrated the highest level of IGF-I and IGF-II expression. Our results suggest autocrine and paracrine effects of the IGFs and their possible involvement in normal eye physiology as well as in the pathogenesis of certain eye diseases. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted