Stem cell transplantation with rehabilitation therapy presents an effective stroke treatment. Here, we discuss current breakthroughs in stem cell research along with rehabilitation strategies that may have a synergistic outcome when combined together after stroke. Indeed, stem cell transplantation offers a promising new approach and may add to current rehabilitation therapies. By reviewing the pathophysiology of stroke and the mechanisms by which stem cells and rehabilitation attenuate this inflammatory process, we hypothesize that a combined therapy will provide better functional outcomes for patients. Using current preclinical data, we explore the prominent types of stem cells, the existing theories for stem cell repair, rehabilitation treatments inside the brain, rehabilitation modalities outside the brain, and evidence pertaining to the benefits of combined therapy. In this review article, we assess the advantages and disadvantages of using stem cell transplantation with rehabilitation to mitigate the devastating effects of stroke. / Revisión por pares

No description available.

No description available.

Stripped-envelope supernovae were thought to be the explosions of very massive stars (& 20 M) that lost their outer layers of hydrogen and/or helium in strong stellar winds. However, recent studies have highlighted that most stripped-envelope supernovae seem to be arising from rela- tively lower-mass progenitor stars in the 12 20 M(sun) range, creating a mystery about the fate of the higher-mass stars. In this licentiate thesis, we review our knowledge of stripped-envelope supernovae, and present the astrophysical problem of their missing high-mass progenitors. The thesis focuses on observations of unique and rare stripped-envelope supernovae classified with modern optical surveys such as the intermediate Palomar Transient Factory (iPTF) and the Public European Southern Observatory Spectroscopic Survey of Transient Objects (PESSTO). In these surveys we have discovered stripped-envelope supernovae with long-lasting broad lightcurves, which are thought to be a marker for highly massive (& 20 M[sun]) progenitor stars. Despite this exciting association, there are only a handful of existing examples of stripped- envelope supernovae with broad lightcurves published in the literature, not numerous enough to account for the missing high-mass stars. During our efforts, the first object we focused on was OGLE-2014-SN-131, a long-lasting supernova in the southern sky initially classified by PESSTO. We re-classified it as a supernova Type Ibn interacting with a helium-rich circumstellar environment. Unlike all other Type Ibn’s in the literature, OGLE-2014-SN-131 was found to have a long rise-time and large lightcurve broadness. By modeling its bolometric lightcurve, we concluded that OGLE-2014-SN-131 must have had an unusually massive progenitor star. Furthermore, since an ordinary radioactive- decay model could not reproduce the lightcurve, we investigated both a magnetar and circum- stellar interaction as potential powering scenarios and favored the latter due to the signatures of interaction present in the spectra. Next, we looked for similar objects in the supernova dataset of the iPTF, which contains over 200 stripped-envelope supernovae. Searching in a sub-sample of 100 well-observed supernovae, we identified 11 to have unusually broad lightcurves. We also constrained the distribution of lightcurve broadness for iPTF stripped-envelope supernovae. The 11 with broad lightcurves will be studied carefully in a forthcoming paper. The first part of this forthcoming paper, which describes the careful statistical identification of these super-novae, is included in this thesis. In it we identify that 10% of the iPTF stripped-envelope supernova sample have broad lightcurves, which a surprisingly high fraction given their rarity in the published literature. Finally, we evaluate whether our estimate of the fraction of broad stripped-envelope supernovae could help explain the missing high-mass progenitors, and con- clude that they can only be a small fraction of the missing high-mass progenitors.

Indiana University-Purdue University Indianapolis (IUPUI) / The innate and adaptive immune responses are critical for host survival. The TNFα/NF-κB signaling pathway is a major regulator of the immune response. The TNFα/NF-κB signaling pathway has also been proposed to play a role in the regulation of hematopoiesis. In the TNFα signaling pathway, full induction of NF-κB (specifically the p65 subunit) dependent transcription is regulated by a co-activator SIMPL. The biological significance of SIMPL in TNFα dependent responses is poorly understood. To study SIMPL in vitro and in vivo in mammalian cells, a knockdown system utilizing shRNA (short hairpin RNA) was used. Analysis of hematopoietic progenitor cells infected with a retrovirus encoding the SIMPL shRNA was used to study the role of SIMPL in hematopoiesis. The ability of progenitor cells lacking SIMPL to grow and differentiate was not compromised. In contrast in the progenitors cells lacking SIMPL, TNFα mediated inhibition of colony formation was significantly enhanced. These growth inhibitory effects of SIMPL were not due to an increase in apoptosis. The enhanced inhibitory affects were specific for TNFα and not found in other common hematopoietic inhibitors (TGF-β1 and IFNγ). Results of this work reveal that SIMPL is a component of the hematopoiesis that is required for TNFα dependent effects upon myeloid progenitors.

Granulocytes represent the first line of defense against bacteria and fungi. Daily production of granulocytes is sustained by steady state granulopoiesis but under stress (e.g., bacterial infection) this program switches to emergency granulopoiesis (EG) which ensures the production of granulocytes at enhanced and accelerated rates. Very little is known about the regulation of EG. In this thesis, we showed that disruption of the β-catenin-TCF/LEF mediated transcription impairs EG in vivo. Further, we demonstrated that lipopolysaccharide (LPS) administration in mice induces accumulation of active β-catenin in hematopoietic stem and progenitor cells (HSPCs) as early as 4 hours (H) after stimulation, with highest increase at 24H. This effect was at least partially mediated in a niche independent manner, since LPS stimulation in vitro induced β-catenin accumulation in c-Kit+ cells after 2H, with a peak activation at 4H. Using single cell RNA sequencing, we determined the cell cluster dynamics of HSPCs following 4H LPS stimulation. Interestingly, we identified a possible upstream activator of β- catenin in one of the clusters - Wnt10b. Indeed, Wnt10b showed a similar expression pattern as EG master regulator Cebpb and β-catenin activation, following in vitro treatment with LPS. Altogether, our data point...

No description available.

<p> Cell therapy for Parkinson's disease will greatly benefit from progress in methods aimed at visualizing the dopamine system and cell replacement techniques. Currently, cell therapy has been met with varied success, in part due to differences in cell sources, transplantation procedures, and our lack of understanding of cell fate post-transplantation. The standardization of transplantation procedures will enhance our ability to draw comparisons between studies and improve cell therapy outcomes. We developed a method to label neural stem/progenitor cells (NSPCs) with technetium-99m and then visualize the cells with single photon emission computed tomography (SPECT) subsequent to grafting in the brain. This labeling method permitted a high uptake of the tracer into the cells without causing damage to the DNA or altering cell viability. The labeling caused a significant decrease (75%) in the proliferative capacity of the SPCs and caused a trend towards an increase in neuronal differentiation. Using this technique paves the way to standardize the location of the transplant and quantify the number transplanted cells while increasing the production of neurons.</p> <p> Experiments were performed to visualize the dopamine system with [(123)I]altropane at pre-and post-transplant time points in the 6-0HDA rat model of Parkinson's disease. [(123)I]altropane binding correlated with the content of dopamine in the stria tum. However, [(123)I]altropane binding was not correlated with dopamine content in the substantia nigra and did not show a correlation with the amphetamine rotations. However, there was a significant correlation with the cylinder test and the postural instability test. When the data was assessed using linear regression, the r^2 value of the linear relationship was low indicating that [(123)I]altropane SPECT is not a good predictor of behavioural outcome due to a weak linear relationship. Our data indicates that [(123)I]altropane predicts the integrity of the striatal dopamine nerve terminals, but does not predict the integrity of the nigrostriatal system. The results are discussed in relation to the use of [(123)I]altropane in comparison to other dopamine SPECT and PET agents. </p> / Thesis / Doctor of Philosophy (PhD)

No description available.

No description available.