Final Scientific/Technical Report

We started to use the first animal model of provoked status epilepticus to test the hypothesis that acute seizures induced by osmotic disruption of the blood-brain barrier result in delayed epileptogenesis. These initial experiments were aimed at perfecting the technique used. One of the problems with the approach used in the past is the fact that intarterial injections are performed across an open incision, which does not allow survival. They have therefore changed the surgical approach as detailed in this paper

»Jugoslawismus« - Aufstieg und Niedergang eines Modells

Wie hat das Modell Jugoslawien eigentlich fanktioniert? Wie konnten die Völker dieses nach dem 1. Weltkrieg geschaffenen Staates mehr als 40 Jahre vergleichsweise friedlich zusammenleben und nun einen grausamen und alle Bindungen zerstörenden Bürgerkrieg führen? Der Nationalismus wird als eine Reaktion auf das Ende des Sozialismus und auf die Schwierigkeiten bei der Einführung des Kapitalismus analysiert: die politisiert die Vergangenheit und historisiert die Gegenwart. Dies ausgerechnet in· einer Zeit, in der die transnationale und mulitethnische Kooperationen zumindest ökonomisch immer wichtiger werden

Jugoslawien - Vom Krieg der Worte zum Krieg der Banden

Der jugoslawische Bürgerkrieg kam für viele Beobachter vollkommen unerwartet und wird mit unfaßbarer Grausamkeit geführt. Die Folgen dieses Kriegs sind nicht abzusehen. Der vorliegende Beitrag schildert die letzten zehn Jahre seine Vorgeschichte, die vom Zeifall der zentralen Behörden im Verlauf einer gleichsam »demokratisierenden Desintegration« über einen »Krieg der Massenmedien« zu einem vielenorts von kaum kontrollierbaren Banden geführten Krieg eskalierte

The role of shear stress in Blood-Brain Barrier endothelial physiology

<p>Abstract</p> <p>Background</p> <p>One of the most important and often neglected physiological stimuli contributing to the differentiation of vascular endothelial cells (ECs) into a blood-brain barrier (BBB) phenotype is shear stress (SS). With the use of a well established humanized dynamic <it>in vitro </it>BBB model and cDNA microarrays, we have profiled the effect of SS in the induction/suppression of ECs genes and related functions.</p> <p>Results</p> <p>Specifically, we found a significant upregulation of tight and adherens junctions proteins and genes. Trans-endothelial electrical resistance (TEER) and permeability measurements to know substances have shown that SS promoted the formation of a tight and highly selective BBB. SS also increased the RNA level of multidrug resistance transporters, ion channels, and several p450 enzymes. The RNA level of a number of specialized carrier-mediated transport systems (e.g., glucose, monocarboxylic acid, etc.) was also upregulated.</p> <p>RNA levels of modulatory enzymes of the glycolytic pathway (e.g., lactate dehydrogenase) were downregulated by SS while those involved in the Krebs cycle (e.g., lactate and other dehydrogenases) were upregulated. Measurements of glucose consumption versus lactate production showed that SS negatively modulated the glycolytic bioenergetic pathways of glucose metabolism in favor of the more efficient aerobic respiration. BBB ECs are responsive to inflammatory stimuli. Our data showed that SS increased the RNA levels of integrins and vascular adhesion molecules. SS also inhibited endothelial cell cycle via regulation of BTG family proteins encoding genes. This was paralleled by significant increase in the cytoskeletal protein content while that of membrane, cytosol, and nuclear sub-cellular fractions decreased. Furthermore, analysis of 2D gel electrophoresis (which allows identifying a large number of proteins per sample) of EC proteins extracted from membrane sub-cellular endothelial fractions showed that SS increased the expression levels of tight junction proteins. In addition, regulatory enzymes of the Krebb's cycle (aerobic glucose metabolism) were also upregulated. Furthermore, the expression pattern of key protein regulators of the cell cycle and parallel gene array data supported a cell proliferation inhibitory role for SS.</p> <p>Conclusions</p> <p>Genomic and proteomic analyses are currently used to examine BBB function in healthy and diseased brain and characterize this dynamic interface. In this study we showed that SS plays a key role in promoting the differentiation of vascular endothelial cells into a truly BBB phenotype. SS affected multiple aspect of the endothelial physiology spanning from tight junctions formation to cell division as well as the expression of multidrug resistance transporters. BBB dysfunction has been observed in many neurological diseases, but the causes are generally unknown. Our study provides essential insights to understand the role played by SS in the BBB formation and maintenance.</p

Akinetic mutism in COVID-19-related encephalopathy: A cytokine-mediated maladaptive sickness behavioral response?

open6sin.a.Pubblicato nella sezione "Viewpoint" della rivistanonePensato, Umberto; Muccioli, Lorenzo; Janigro, Damir; Guarino, Maria; Bisulli, Francesca; Cortelli, PietroPensato, Umberto; Muccioli, Lorenzo; Janigro, Damir; Guarino, Maria; Bisulli, Francesca; Cortelli, Pietr

The Etiological Role of Blood-Brain Barrier Dysfunction in Seizure Disorders

A wind of change characterizes epilepsy research efforts. The traditional approach, based on a neurocentric view of seizure generation, promoted understanding of the neuronal mechanisms of seizures; this resulted in the development of potent anti-epileptic drugs (AEDs). The fact that a significant number of individuals with epilepsy still fail to respond to available AEDs restates the need for an alternative approach. Blood-brain barrier (BBB) dysfunction is an important etiological player in seizure disorders, and combination therapies utilizing an AED in conjunction with a “cerebrovascular” drug could be used to control seizures more effectively than AED therapy alone. The fact that the BBB plays an etiologic role in other neurological diseases will be discussed in the context of a more “holistic” approach to the patient with epilepsy, where comorbidity variables are also encompassed by drug therapy

Serum S100B: A Potential Biomarker for Suicidality in Adolescents?

Background: Studies have shown that patients suffering from depression or schizophrenia often have immunological alterations that can be detected in the blood. Others reported a possible link between inflammation, a microgliosis and the blood-brain barrier (BBB) in suicidal patients. Serum S100B is a marker of BBB function commonly used to study cerebrovascular wall function. Methods: We measured levels of S100B in serum of 40 adolescents with acute psychosis, 24 adolescents with mood disorders and 20 healthy controls. Patients were diagnosed according to DSM-IV TR criteria. We evaluated suicidal ideation using the suicidality subscale of the Brief Psychiatric Rating Scale for Children (BPRS-C). Results: Serum S100B levels were significantly higher (p,0.05) and correlated to severity of suicidal ideation in patients with psychosis or mood disorders, independent of psychiatric diagnosis. Patients with a BPRS-C suicidality subscores of 1–4 (low suicidality) had mean serum S100B values +/2 SEM of 0.152+/20.020 ng/mL (n = 34) compared to those with BPRS-C suicidality subscores of 5–7 (high suicidality) with a mean of 0.354+/20.044 ng/mL (n = 30). This difference was statistically significant (p,0.05). Conclusion: Our data support the use of S100B as an adjunctive biomarker to assess suicidal risk in patients with mood disorders or schizophrenia

Peripheral Blood and Salivary Biomarkers of Blood-Brain Barrier Permeability and Neuronal Damage:Clinical and Applied Concepts

International audienceWithin the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings

Evaluation of Nintendo Wii Balance Board as a Tool for Measuring Postural Stability After Sport-Related Concussion

Recent changes to postconcussion guidelines indicate that postural-stability assessment may augment traditional neurocognitive testing when making return-to-participation decisions. The Balance Error Scoring System (BESS) has been proposed as 1 measure of balance assessment. A new, freely available software program to accompany the Nintendo Wii Balance Board (WBB) system has recently been developed but has not been tested in concussed patients