Intracarotid administration of human bone marrow mononuclear cells in rat photothrombotic ischemia

Background: Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction. So far only small pilot trials tested the effects of cell therapy in stroke patients, whereas large clinical trials were conducted in patients with ischemic heart disease. To investigate the therapeutic benefit of cell therapy to improve the recovery after stroke, we determined the efficacy of bone marrow derived mononuclear cells, which were shown to improve the recovery in experimental and clinical acute myocardial infarction studies, in a rat stroke model. Methods: Adult male Wistar rats were randomly assigned to receive either five million human bone marrow mononuclear cells (hBMC) or placebo intraarterially 3 days after photothrombotic ischemia. For immunosuppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24 hours before the cell transplantation. A battery of behavioural tests was performed before and up to 4 weeks after ischemia. Results: Body temperature and body weight revealed no difference between groups. Neurological deficits measured by the Rotarod test, the adhesive-removal test and the cylinder test were not improved by hBMC transplantation compared to placebo. Conclusions: This study demonstrates that hBMC do not improve functional recovery when transplanted intraaterially 3 days after the onset of focal cerebral ischemia. A possible reason for the failed neurological improvement after cell therapy might be the delayed treatment initiation compared to other experimental stroke studies that showed efficacy of bone marrow mononuclear cells

Erythropoietin for stroke treatment: dead or alive?

Endothelial progenitor cell (EPC) mobilization from the bone marrow was considered to improve outcome after ischemic stroke. Erythropoietin (EPO) might be a potential candidate stroke drug that increases the number of circulating EPCs. In the previous issue of Critical Care, Yip and colleagues investigated the effect of EPO in stroke patients on both clinical outcome and EPC stimulation. Although beneficial effects of EPO were observed, several issues regarding EPO's suitability as a stroke drug remain

Case Study of Holistic Energy Management Using Genetic Algorithms in a Sliding Window Approach

Energy management systems are used to find a compromise between conflicting goals that can be identified for battery electric vehicles. Typically, these are the powertrain efficiency, the comfort of the driver, the driving dynamics, and the component aging. This paper introduces an optimization-based holistic energy management system for a battery electric vehicle. The energy management system can adapt the vehicle velocity and the power used for cabin heating, in order to minimize the overall energy consumption, while keeping the total driving time and the cabin temperature within predefined limits. A genetic algorithm is implemented in this paper. The approach is applied to different driving cycles, which are optimized by dividing them into distinctive time frames. This approach is referred to as the sliding window approach. The optimization is conducted with two separate driving cycles, the New European Driving Cycle (NEDC) and a recorded real-world drive. These are analyzed with regard to the aspects relevant to the energy management system, and the optimization results for the two cycles are compared. The results presented in this paper demonstrate the feasibility of the sliding window approach. Moreover, they reveal the differences in fundamental parameters between the NEDC and the recorded drive and how they affect the optimization results. The optimization leads to an overall reduction in energy consumption of "inline-formula" "math display="inline"" "semantics" "mrow" "mn"3.37"/mn" "mo"%"/mo" "/mrow" "/semantics" "/math" "/inline-formula" for the NEDC and "inline-formula" "math display="inline"" "semantics" "mrow" "mn"3.27"/mn" "mo"%"/mo" "/mrow" "/semantics" "/math" "/inline-formula" for the recorded drive, without extending the travel time. Document type: Articl

Experimental RNomics in Aquifex aeolicus: identification of small non-coding RNAs and the putative 6S RNA homolog

By an experimental RNomics approach, we have generated a cDNA library from small RNAs expressed from the genome of the hyperthermophilic bacterium Aquifex aeolicus. The library included RNAs that were antisense to mRNAs and tRNAs as well as RNAs encoded in intergenic regions. Substantial steady-state levels in A.aeolicus cells were confirmed for several of the cloned RNAs by northern blot analysis. The most abundant intergenic RNA of the library was identified as the 6S RNA homolog of A.aeolicus. Although shorter in size (150 nt) than its γ-proteobacterial homologs (∼185 nt), it is predicted to have the most stable structure among known 6S RNAs. As in the γ-proteobacteria, the A.aeolicus 6S RNA gene (ssrS) is located immediately upstream of the ygfA gene encoding a widely conserved 5-formyltetrahydrofolate cyclo-ligase. We identifed novel 6S RNA candidates within the γ-proteobacteria but were unable to identify reasonable 6S RNA candidates in other bacterial branches, utilizing mfold analyses of the region immediately upstream of ygfA combined with 6S RNA blastn searches. By RACE experiments, we mapped the major transcription initiation site of A.aeolicus 6S RNA primary transcripts, located within the pheT gene preceding ygfA, as well as three processing sites

Die deutsche Frage - Problemskizze und Thesen

Wohl mit keinem anderen Problem hat sich die marxistische Arbeiterbewegung so schwer getan wie mit dem der Nation. Die Annalen des Sozialismus und Kommunismus sind gefüllt mit unbewältigten theoretischen und praktischen Problemen im Umfeld des Begriffspaars Klasse-Nation, und Deutschland macht darin keine Ausnahme. Im Gegenteil: wenn schon ganz allgemein nicht von der marxistisch-sozialistischen Theorie der Nation gesprochen werden kann, so ergeben sich aus den Besonderheiten der deutschen Geschichte ganz spezifische Hindernisse für eine unbefangene Diskussion der nationalen Problematik auf der Linken. Eine sozialistische Analyse der »Deutschen Frage« nach 1945 muss sich deshalb zunächst auch der Frage stellen, welcher theoretische Nationen begriff und welches Verständnis der Nationalgeschichte Deutschlands ihr zugrundeliegen

Nirgendwo-Sozialismus: Eine Replik von Peter Brandt und Günter Minnerup

Die Schwierigkeit, auf die Polemik von Frank Dinge! gegen unseren Artikel zur »Deutschen Frage« zu antworten, liegt weniger in den Differenzen zwischen ihm und uns bezüglich unserer konkreten Einschätzung der deutschen Situation, als in den diametral entgegengesetzten Grundhaltungen zum Problemfeld Nation, Nationalismus, nationale Identität und damit - wie wir zeigen werden - unterschiedlichen Begriffen von sozialistischer Politik. So könnte man vortrefflich darüber diskutieren, wie die Biermannsche Aufforderung zur »Einheit der Linken in Ost und West« mit sinnvollem Inhalt zu füllen oder inwieweit eine Abkoppelung der beiden deutschen Staaten von ihren jeweiligen Paktsystemen wünschenswert oder möglich sei, wenn es nicht diese grundlegenden Verständnisschwierigkeiten gäbe. Wir wollen gern zugeben, daß die aus Platzgründen notwendige Kompression unserer theoretischen und historischen Argumentation gelegentlich Mißve·rständnissen Vorschub geleistet haben mag. Nur mit Mißverständnissen jedoch ist ein derartiges Ausmaß an Verständnislosigkeit für unser Anliegen, wie es Dinge! artikuliert, schwer zu erklären

The dilemma of neuroprotection trials in times of successful endovascular recanalization.

BACKGROUND The "translational roadblock" between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution. METHODS To verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study. For animal data, we systematically searched pubmed to identify all rodent studies, in which stroke was induced by MCAO and at least two sequential MRI scans were performed for infarct volume assessment within the first two days. For clinical data, we included 107 consecutive stroke patients with large artery occlusion, who received MRI scans upon admission and one or two days later. RESULTS Our preclinical meta-analyses included 50 studies with 676 animals. Untreated animals had a median post-reperfusion infarct volume growth of 74%. Neuroprotective treatments reduced this infarct volume growth to 23%. A retrospective clinical cohort study showed that stroke patients had a median infarct volume growth of only 2% after successful recanalization. Stroke patients with unsuccessful recanalization, by contrast, experienced a meaningful median infarct growth of 148%. CONCLUSION Our study shows that rodents have a significant post-reperfusion infarct growth, and that this post-reperfusion infarct growth is the target of neuroprotective treatments. Stroke patients with successful recanalization do not have such infarct growth and thus have no target for neuroprotection

Monocyte Chemoattractant Protein-1-Deficiency Impairs the Expression of IL-6, IL-1β and G-CSF after Transient Focal Ischemia in Mice

Monocyte chemoattractant protein-1 (MCP-1), a chemokine secreted by neurons and astrocytes following stroke is known to aggravate ischemia-related damage. Previous studies revealed that MCP-1-deficient mice develop smaller infarcts and have an improved neurological outcome, whereas mice overexpressing MCP-1 show worsened brain damage and impaired neurological function. The aim of the present study was to elucidate the molecular background of the enhanced recovery in MCP-1-deficient mice after stroke. For this purpose, we (1) performed expression analyses on crucial post-stroke related inflammatory genes in MCP-1-deficient mice compared to wildtype controls, (2) analyzed a possible impact of MCP-1 on astrocyte activation (3) investigated the cellular origin of respective inflammatory cytokines and (4) analyzed the impact of MCP-1 secretion on the migration of both neutrophil granulocytes and T-cells. Here we report that MCP-1-deficiency leads to a shift towards a less inflammatory state following experimental occlusion of the middle cerebral artery including an impaired induction of interleukin-6, interleukin-1β and granulocyte-colony stimulating factor expression as well as a subsequent diminished influx of hematogenous cells. Additionally, MCP-1-deficient mice developed smaller infarcts 36 hours after experimental stroke. Investigations revealed no differences in transcription of tumor necrosis factor-α and astrogliosis 12 and 36 hours after onset of ischemia. These novel results help to understand post ischemic, inflammatory mechanisms and might give further arguments towards therapeutical interventions by modulation of MCP-1 expression in post stroke inflammation