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Warunya Woranush,1,2 Mats Leif Moskopp,2,3 Annahita Sedghi,1 Isabella Stuckart,1 Thomas Noll,2 Kristian Barlinn,1 Timo Siepmann1 1Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 2Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 3Vivantes Klinikum im Friedrichshain, Charité Academic Teaching Hospital, Klinik für Neurochirurgie, Berlin, GermanyCorrespondence: Timo SiepmannDepartment of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetschertstr. 74, Dresden, 01309, GermanyTel +49 175-613-14546Email timo.siepmann@ukdd.dePurpose: Post-stroke depression (PSD) occurs in one-third of stroke survivors, leading to a substantial decrease in quality of life as well as delayed functional and neurological recovery. Early detection of patients at risk and initiation of tailored preventive measures may reduce the medical and socioeconomic burden associated with PSD. We sought to review the current evidence on pharmacological and non-pharmacological prevention of PSD.Materials and Methods: We conducted a systematic review using PubMed/MEDLINE and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including randomized controlled studies. Eligible studies were included when performed within 1 year after the index cerebrovascular event. Animal and basic research studies, studies lacking a control group, review papers, and case reports were excluded.Results: Out of 150 studies screened, 37 met our criteria. Among the strategies identified, administration of antidepressants displayed the most robust evidence for preventing PSD, whereas non-pharmacological interventions such as psychotherapy appear to be the most frequently used approaches to prevent depression after stroke. Research suggests that the efficacy of PSD prevention increases with the duration of preventive treatment. Seven out of 11 studies (63%) that used pharmacological and eight out of 16 (50%) that used non-pharmacological interventions reported a positive preventive effect on PSD.Conclusion: Overall, the current literature on PSD prevention shows heterogeneity, substantiating a need for well-designed randomized controlled trials to test the safety and efficacy of pharmacological as well as non-pharmacological and composite prevention regimens to minimize the risk of PSD in stroke survivors. Integrative strategies combining personalized non-pharmacological interventions such as educational, mental, and physical health support, and pharmacological strategies such as SSRIs may be the most promising approach to prevent PSD.Keywords: PSD, antidepressant, depression, prevention, stroke

In today's teaching and learning approaches for first-semester students, practical courses more and more often complement traditional theoretical lectures. This practical element allows an early insight into the real world of engineering, augments student motivation, and enables students to acquire soft skills early. This paper describes a new freshman introduction course into practical engineering, which has been established within the Bachelor of Science curriculum of Electrical Engineering and Information Technology of RWTH Aachen University, Germany. The course is organized as an eight-day, full-time block laboratory for over 300 freshman students, who were supervised by more than 60 tutors from 23 institutes of the Electrical Engineering Department. Based on a threefold learning concept comprising mathematical methods, MATLAB programming, and practical engineering, the students were required to transfer mathematical basics to algorithms in MATLAB in order to control LEGO Mindstorms robots. Toward this end, a new toolbox, called the "RWTH-Mindstorms NXT Toolbox," was developed, which enables the robots to be controlled remotely via MATLAB from a host computer. This paper describes how the laboratory course is organized and how it induces students to think as actual engineers would in solving real-world tasks with limited resources. Evaluation results show that the project improves the students' MATLAB programming skills, enhances motivation, and enables a peer learning process. (Contains 15 figures.)

Ischemia-induced apoptosis of endothelial cells may contribute to tissue injury, organ failure, and transplantation rejection. However, little is known about survival mechanisms capable to counteract endothelial apoptosis. This study investigated the potential role of an endogenous anti-apoptotic response elicited by transient hypoxia, capable to avert ongoing apoptosis in endothelial cells. Experiments were carried out in three different types of cultured endothelial cells (human umbilical vein, pig aorta, and from rat coronary microvasculature). As a pro-apoptotic challenge endothelial cells were cultured in serum-free medium and subjected to hypoxia for 2 h. We found that transient hypoxia reduced caspase 3 activation within 1 h of hypoxia. Accordingly, the number of apoptotic cells was reduced after 24 h of reoxygenation. This was true for all three cell types analyzed. Analysis of Akt and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways revealed that hypoxia induced a transient activation of ERK 2 but not of Akt. ERK 2 phosphorylation preceded the phosphorylation of pro-apoptotic molecule Bad at Ser112, an inhibitory phosphorylation site specific for ERK. The protective effects of hypoxia regarding Bad phosphorylation, caspase 3 activation, and apoptosis were abolished by MEK 1/2 inhibitors, PD98059 or UO126, as well as by antisense oligonucleotides directed against ERK 1/2. Furthermore, inhibition of this pathway inhibited hypoxia-induced increase in mitochondrial membrane potential. The present study demonstrates that transient hypoxia induces a novel survival mechanism that protects endothelial cells against apoptosis. This endogenous process involves MEK/ERK-mediated inhibition of the pro-apoptotic molecule Bad and caspase 3. anti-apoptosis; Bad; extracellular signal-regulated kinases; phosphoinositide 3-kinase/Akt doi: 10.1152/ajpcell.00333.2009.

Opposite effect of cAMP signaling in endothelial barriers of different origin. Am J Physiol Cell Physiol 287: C1246-C1255, 2004; doi: 10.1152/ajpcell.00132.2004.--cAMP-mediated signaling mechanisms may destabilize or stabilize the endothelial barrier, depending on the origin of endothelial cells. Here, microvascular coronary [coronary endothelial cells (CEC)] and macrovascular aortic endothelial cell (AEC) monolayers with opposite responses to cAMP were analyzed. Macromolecule permeability, isometric force, activation state of contractile machinery [indicated by phosphorylation of regulatory myosin light chains (MLC), activity of MLC kinase, and MLC phosphatase], and dynamic changes of adhesion complex proteins (translocation of VE-cadherin and paxillin) were determined, cAMP signaling was stimulated by the adenosine receptor agonist 5'-N-(ethylcarboxamido)-adenosine (NECA), the [beta]-adrenoceptor agonist isoproterenol (Iso), or by the adenylyl cyclase activator forskolin (FSK). Permeability was increased in CEC and decreased in AEC on stimulation with NECA, Iso, or FSK. The effects could be inhibited by the PKA inhibitor Rp-8-CPT-cAMPS and imitated by the PKA activator Sp-cAMPS. Under cAMP/PKA-dependent stimulation, isometric force and MLC phosphorylation were reduced in monolayers of either cell type, due to an activation of MLC phosphatase. In CEC but not in AEC, FSK induced delocalization of VE-cadherin and paxillin from cellular adhesion complexes as indicated by cell fractionation and immunofluorescence microscopy. In conclusion, decline in contractile activation and isometric force contribute to cAMP/PKA-mediated stabilization of barrier function in AEC. In CEC, this stabilizing effect is overruled by cAMP-induced disintegration of cell adhesion structures. endothelial cell adhesion; endothelial permeability; isometric force; myosin light chain kinase; myosin light chain pbosphatase

Klingenberg, D., D. Gunduz, F. Hartel, K. Bindewald, M. Schafer, H. M. Piper, and T. Noll. MEK/MAPK as a signaling element in ATP control of endothelial myosin light chain. Am J Physiol Cell Physiol 286: C807-C812, 2004; 10.1152/ajpcell.00002.2003.--Phosphorylation of endothelial myosin light chains (MLC) is a key mechanism in control of endothelial contractile machinery. Extracellular ATP influences endothelial MLC phosphorylation by either activation of [Ca.sup.2+] -dependent MLC kinase or [Ca.sup.2+]-independent MLC phosphatase. Here, the role of the MEK/MAPK pathway in this signaling was investigated in porcine aortic endothelial cells. Phosphorylation of ERK2 and phosphorylation of MLC were analyzed in cultured aortic endothelial cells. ATP (10 [micro]M) increased ERK2 phosphorylation from basal 17 [+ or -] 3 to 53 [+ or -] 4%, an effect suppressed in the presence of the MEK inhibitors PD-98059 (20 [micro]M) or U0126 (10 [micro]M). Phosphorylation of ERK2 was not dependent on the ATP-induced cytosolic [Ca.sup.2+] rise, because it was unaltered when this was suppressed by the [Ca.sup.2+] chelator BAPTA (10 [micro]M) or xestospongin C (3 [micro]M), an inhibitor of the inositol 1,4,5 trisphosphate-sensitive [Ca.sup.2+] release mechanism of the endoplasmic reticulum. Phosphorylation of ERK2 was neither induced by the adenosine analog 5'-(N-ethylcarboxamido)adenosine (l [micro]M) nor inhibited in the presence of the adenosine receptor antagonist 8-phenyltheophylline (10 [micro]M). ATP increased MLC kinase activity, and this was blocked in presence of PD-98059. ATP also increased MLC phosphatase activity, which was not inhibited by PD-98059. The MEK/MAPK pathway is a [Ca.sup.2+] -independent part of ATP signaling toward MLC kinase but not of ATP signaling toward MLC phosphatase. mitogen-activated protein kinase; contractile machinery; myosin light chain kinase; myosin light chain phosphatase

An investigation of the relationship of the progression of hyperpermeability of endothelial monolayers during the initial state of energy to the delocalization of vinculin from adhesion complexes was conducted. The vinculin localization and phosphorylation, protein kinase C activity and albumen permeability were examined in cultured coronary endothelial monolayers from rats. Results indicated that vinculin phosphorylation is involved in the development of hyperpermeability during energy depletion in coronary endothelial monolayers.