Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.

Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain¿s white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrowderived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft

Malignant Profile Detected by CT Angiographic Information Predicts Poor Prognosis despite Thrombolysis within Three Hours from Symptom Onset

Objective: A malignant profile of early brain ischemia has been demonstrated in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) trial. Patients with a malignant profile had a low chance for an independent functional outcome despite thrombolysis within 3–6 h. We sought to determine whether CT angiography (CTA) could identify a malignant imaging profile within 3 h from symptom onset. Methods: We studied consecutive patients (04/02–09/07) with anterior circulation stroke who received CTA before intravenous thrombolysis within 3 h. We assessed the Alberta Stroke Program Early CT Score (ASPECTS) on CTA source images (CTASI). Intracranial thrombus burden on CTA was assessed with a novel 10-point clot burden score (CBS). We analyzed percentages independent (modified Rankin Scale score ≤2) and fatal outcome at 3 months and parenchymal hematoma rates across categorized combined CTASI-ASPECTS + CBS score groups where 20 is best and 0 is worst. Results: We identified 114 patients (median age 73 years [interquartile range 61–80], onset-to-tPA time 129 min [95–152]). Among 24 patients (21%) with extensive hypoattenuation on CTASI and extensive thrombus burden (combined score ≤10), only 4% (1/24) were functionally independent whereas mortality was 50% (12/24). In contrast, 57% (51/90) of patients with less affected scores (combined score 11–20) were functionally independent and mortality was 10% (9/90; p < 0.001). Parenchymal hematoma rates were 30% (7/23) vs. 8% (7/88), respectively (p = 0.008). Conclusion: CTA identifies a large hyperacute stroke population with high mortality and low likelihood for independent functional outcome despite early thrombolysis.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Implementation and Test of a 48 v Smart Battery System with Integrated DC/DC Converter

Advances in battery system design, integration and management help to meet the highly demanding safety requirements for Li-ion batteries in the electric mobility field. The aim of this paper is to describe the implementation of a new smart battery, based on the concept of smart cells combined with an FPGA-based main unit and an embedded DC/DC converter. An extended test campaign has been carried out to verify the correct and effective operation of all the battery components. The paper shows that innovative battery functions can be achieved by the integration of up-to-date electronics technology