From Autonomic Nervous System Evaluation to a Novel Paradigm for Scientific Research, Clinical Practice and Economic Development

[No abstract available

Pre-ictal heart rate variability alterations in focal onset seizures and response to vagus nerve stimulation

Purpose: Vagus nerve stimulation (VNS) is an effective and well-known treatment for drug resistant epilepsy (DRE) patients since 1997, yet prediction of treatment response before implantation is subject of ongoing research. Neuroimaging and neurophysiological studies investigating the vagal afferent network in resting state documented that differences in between epilepsy patients were related to treatment response. This study investigated whether an event-related parameter, pre-ictal heart rate variability (HRV) is associated with response to VNS therapy. Methods: DRE patients underwent video-electroencephalography (EEG) recording before VNS implantation. HRV parameters (time, non-linear and frequency domain) were assessed for every seizure during two 10 min time frames: baseline (60 min before seizure onset) and pre-ictal (10 min before seizure onset). Pre-ictal HRV parameter alterations were correlated with VNS response after one year of VNS therapy and seizure characteristics (temporal/extratemporal, left/right or bilateral). Results: 104 seizures from 22 patients were evaluated. Eleven patients were VNS responders with a seizure frequency reduction of > 50 % after one year of VNS. In VNS responders no changes in HRV parameters were found while in VNS non-responders the time domain and non-linear HRV variables decreased significantly (p = 0.024, p = 0.005, p = 0.005) during the pre-ictal time frame. 10/11 VNS non-responders had a seizure lateralization to the left compared to 4/11 VNS responders. Conclusion: VNS non-responders were characterized by a significant decrease of pre-ictal HRV (time domain/nonlinear variables) suggesting a sudden autonomic imbalance probably due to an impaired central autonomic function that makes it at the same time unlikely to respond to VNS

Recent developments of disease and human in vitro models of the blood-brain barrier

Many different in-vitro models of the BBB have been published based on primary cells, immortalized cell lines or tumor cells derived from several species such as bovine, porcine, mouse, rat or even human. However, no standard in-vitro model of the blood-brain barrier (BBB) is established nor broadly accepted, although huge demands from basic research as well as pharmaceutical industry exist. Moreover, there is a great need for validated disease in-vitro models of the blood-brain barrier considering that almost in every neurodegenerative illness the BBB is altered which presumably contributes to the disease’s etiology and progression. The lack of human BBB models mimicking the in-vivo situation close enough is dramatic, especially considering species differences and the need for save data transferability from e.g. rodent preclinical models to the human situation. After the introduction about the BBB and its role in different diseases two novel BBB in-vitro models will be explained in more detail. First, a mouse BBB in-vitro model for ischemia will be introduced comprising characteristics of barrier breakdown, ABC-transporter functionality, morphology and cerebral ischemia relevant enzyme activities by qPCR, western blotting, immunofluorescence microscopy and functional assays [1]. This model was used to investigate therapeutic strategies. Cross-correlation with a mouse model of traumatic brain injury confirmed the usability and most importantly the predictability of the in-vitro model. Second, recent developments of stem cell models highlight the potential to generate human in-vitro BBB models with in-vivo like phenotype paired with high paracellular tightness. As example for this trend a novel human blood-brain barrier in-vitro model will be introduced this is based on cells derived from human induced pluripotent stem cells. In summary, current works show that the development of predictive disease and human in-vitro models of the BBB is feasible and further comprehensive studies may pave the way for these models to reduce the number of animal studies

Umwelt und Beschaeftigung Strategien fuer eine nachhaltige Entwicklung und deren Auswirkungen auf die Beschaeftigung

'Die Untersuchung hat zum Ziel, auf Grundlage einer Bestandsaufnahme der Beschaeftigungssituation im Umweltschutzbereich, der grossteils noch immer von nachsorgenden Aktivitaeten dominiert wird, sowie einer Analyse existierender Anwendungen des integrierten Umweltschutzes auf betrieblicher Ebene, die quantitativen und qualitativen Auswirkung eines moeglichen, schrittweisen Uebergangs zu einem nachhaltigen Wirtschaftssystem darzustellen. Nur durch die Betrachtung der quantitativen und qualitativen Effekte kann den Nachhaltigkeitsanforderungen im Dreieck Umwelt-Wirtschaft-Soziales entsprochen werden. Diese Arbeit untersucht jedoch nur Effizienzansaetze, z.B. die Herstellung des gleichen Gutes mit weniger Ressourcen und Belastungen. Nicht untersucht werden andere Nachhaltigkeitspolitiken (Suffizienz), die etwa auf das Ersetzen eines 'koerperlichen' (stofflichen) Produktes durch eine Dienstleistung abzielen. Auch werden grundsaetzliche Aenderungen der vorherrschenden Produktions- und Konsummuster nicht untersucht, da der Fokus ausschliesslich auf technischorganisatorischen Massnahmen des integrierten Umweltschutzes auf betrieblicher Ebene (Oeko-Effizienz des Produktionsprozesses) liegt. Dabei werden Informationen aus folgenden Laendern der Europaeischen Union herangezogen bzw. im Rahmen der Studie erarbeitet: Deutschland, Niederlande, Schweden, Spanien und Oesterreich. Aus den Ergebnissen dieser empirischen Analyse werden moegliche Entwicklungstendenzen abgeschaetzt, die sich aus einer verbreiteten Diffusion integrierter Umweltschutzpraktiken ergeben; im Mittelpunkt der Studie stehen jedoch Schlussfolgerungen ueber Integrationsmoeglichkeiten beschaeftigungs- und umweltpolitischer Inteventionen der Europaeischen Union bzw. ihrer Mitgliedstaaten.' (Autorenreferat)Available from IAB-90-1EG0-116400 BL 432 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

The pivotal role of astrocytes in an in vitro stroke model of the blood-brain barrier

Stabilization of the blood-brain barrier during and after stroke can lead to less adverse outcome. For elucidation of underlying mechanisms and development of novel therapeutic strategies validated in vitro disease models of the blood-brain barrier could be very helpful. To mimic in vitro stroke conditions we have established a blood-brain barrier in vitro model based on mouse cell line cerebEND and applied oxygen/glucose deprivation (OGD). The role of astrocytes in this disease model was investigated by using cell line C6. Transwell studies pointed out that addition of astrocytes during OGD increased the barrier damage significantly in comparison to the endothelial monoculture shown by changes of transendothelial electrical resistance as well as fluorescein permeability data. Analysis on mRNA and protein levels by qPCR, western blotting and immunofluorescence microscopy of tight junction molecules claudin-3,-5,-12, occludin and ZO-1 revealed that their regulation and localisation is associated with the functional barrier breakdown. Furthermore, soluble factors of astrocytes, OGD and their combination were able to induce changes of functionality and expression of ABC-transporters Abcb1a (P-gp), Abcg2 (bcrp), and Abcc4 (mrp4). Moreover, the expression of proteases (matrixmetalloproteinases MMP-2, MMP-3, MMP-9, and t-PA) as well as of their endogenous inhibitors (TIMP-1, TIMP-3, PAI-1) was altered by astrocyte factors and OGD which resulted in significant changes of total MMP and t-PA activity. Morphological rearrangements induced by OGD and treatment with astrocyte factors were confirmed at a nanometer scale using atomic force microscopy. In conclusion, astrocytes play a major role in blood-brain barrier breakdown during OGD in vitro