Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice

Background: Stroke models are essential tools in experimental stroke. Although several models of stroke have been developed in a variety of animals, with the development of transgenic mice there is the need to develop a reliable and reproducible stroke model in mice, which mimics as close as possible human stroke. Methods: BALB/Ca-RAG2-/-gc-/- mice were subjected to cauterization or thrombosis stroke model and sacrificed at different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell proliferation in the SVZ. Brains were processed for immunohistochemical and EM. Results: In both stroke models, after inflammation the same glial scar formation process and damage evolution takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces activation of SVZ proliferation. Conclusions: Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis, tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and regeneration. Moreover, this stroke model in RAG 2-/- gC -/- allows cell transplant from different species, even human, to be analyzed

Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice

Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/-) γC(-/-) mice subjected to FeCl(3) thrombosis mediated stroke were intracranially injected with 2 × 10(5) hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ) and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of strok

Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice

Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/-) γC(-/-) mice subjected to FeCl(3) thrombosis mediated stroke were intracranially injected with 2 × 10(5) hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ) and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of strok