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Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging, and investigational cell-based therapies.

Canazza A, Minati L, Boffano C, Parati E, Binks S - Front Neurol (2014)

Bottom Line: Realistic experimental animal models are crucial to understand the mechanisms of neuronal survival following ischemic brain injury and to develop therapeutic interventions.In parallel, advancements in imaging techniques permit better mapping of the spatial-temporal evolution of the lesioned cortex and its functional responses.This review provides a condensed conceptual review of the state of the art of this field, from models and magnetic resonance imaging techniques through to stem cell therapies.

View Article: PubMed Central - PubMed

Affiliation: Cerebrovascular Diseases Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta" , Milan , Italy.

ABSTRACT
Stroke continues to be a significant cause of death and disability worldwide. Although major advances have been made in the past decades in prevention, treatment, and rehabilitation, enormous challenges remain in the way of translating new therapeutic approaches from bench to bedside. Thrombolysis, while routinely used for ischemic stroke, is only a viable option within a narrow time window. Recently, progress in stem cell biology has opened up avenues to therapeutic strategies aimed at supporting and replacing neural cells in infarcted areas. Realistic experimental animal models are crucial to understand the mechanisms of neuronal survival following ischemic brain injury and to develop therapeutic interventions. Current studies on experimental stroke therapies evaluate the efficiency of neuroprotective agents and cell-based approaches using primarily rodent models of permanent or transient focal cerebral ischemia. In parallel, advancements in imaging techniques permit better mapping of the spatial-temporal evolution of the lesioned cortex and its functional responses. This review provides a condensed conceptual review of the state of the art of this field, from models and magnetic resonance imaging techniques through to stem cell therapies.

No MeSH data available.


Related in: MedlinePlus

Representative tetrazolium chloride strained sections of ischemic mice treated with vehicle (left panel), adipose stem cells (ASC, central panel) and bone marrow stem cells (BMSC, right panel). Reproduced from Ref. (168) by permission of Informa Healthcare Inc.
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Figure 5: Representative tetrazolium chloride strained sections of ischemic mice treated with vehicle (left panel), adipose stem cells (ASC, central panel) and bone marrow stem cells (BMSC, right panel). Reproduced from Ref. (168) by permission of Informa Healthcare Inc.

Mentions: An alternative and plentiful source of adult MSCs is adipose tissue, which is accessible with a potential supply via liposuction procedures (134, 135). It poses fewer ethical challenges than embryonic sources and adipose-derived stem cells (ASC) may have greater potency in regenerative settings than other cell types. A murine study of ischemic stroke therapy highlighted a 1000-fold richer density of MSCs in adipose tissue compared to BM, and ASCs are known to expand more efficiently than BM stem cells of equivalent density and proliferation index (9, 168, 169). Ikegame and colleagues (168) found that after 48 h in culture, ASCs secreted higher levels of growth factors including hepatocyte growth factor (HGF) than BMSCs. In vivo experiments supported this ASC potential, demonstrating both improved functional performance and higher quantities of growth factors and smaller lesion size on neuropathological samples of ASC compared to BMSC-treated mice (Figure 5). As in other studies, the transplanted cells did not thrive as none were detected in histological analysis of the infarct at 24 h, again suggesting gains are due to trophic influences and even that transplanted cells may not differentiate conclusively into mature neural lineages (168, 169). In addition to positive experimental effects, since ASCs offer options of autologous harvesting and bear low potential for immunological reactions, their investigation as stroke therapy should certainly continue. However, long-term safety studies are vital before clinical implementation, as secretion of trophic factors and indeed tumorigenicity of MSCs may create risk of neoplasm (170).


Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging, and investigational cell-based therapies.

Canazza A, Minati L, Boffano C, Parati E, Binks S - Front Neurol (2014)

Representative tetrazolium chloride strained sections of ischemic mice treated with vehicle (left panel), adipose stem cells (ASC, central panel) and bone marrow stem cells (BMSC, right panel). Reproduced from Ref. (168) by permission of Informa Healthcare Inc.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928567&req=5

Figure 5: Representative tetrazolium chloride strained sections of ischemic mice treated with vehicle (left panel), adipose stem cells (ASC, central panel) and bone marrow stem cells (BMSC, right panel). Reproduced from Ref. (168) by permission of Informa Healthcare Inc.
Mentions: An alternative and plentiful source of adult MSCs is adipose tissue, which is accessible with a potential supply via liposuction procedures (134, 135). It poses fewer ethical challenges than embryonic sources and adipose-derived stem cells (ASC) may have greater potency in regenerative settings than other cell types. A murine study of ischemic stroke therapy highlighted a 1000-fold richer density of MSCs in adipose tissue compared to BM, and ASCs are known to expand more efficiently than BM stem cells of equivalent density and proliferation index (9, 168, 169). Ikegame and colleagues (168) found that after 48 h in culture, ASCs secreted higher levels of growth factors including hepatocyte growth factor (HGF) than BMSCs. In vivo experiments supported this ASC potential, demonstrating both improved functional performance and higher quantities of growth factors and smaller lesion size on neuropathological samples of ASC compared to BMSC-treated mice (Figure 5). As in other studies, the transplanted cells did not thrive as none were detected in histological analysis of the infarct at 24 h, again suggesting gains are due to trophic influences and even that transplanted cells may not differentiate conclusively into mature neural lineages (168, 169). In addition to positive experimental effects, since ASCs offer options of autologous harvesting and bear low potential for immunological reactions, their investigation as stroke therapy should certainly continue. However, long-term safety studies are vital before clinical implementation, as secretion of trophic factors and indeed tumorigenicity of MSCs may create risk of neoplasm (170).

Bottom Line: Realistic experimental animal models are crucial to understand the mechanisms of neuronal survival following ischemic brain injury and to develop therapeutic interventions.In parallel, advancements in imaging techniques permit better mapping of the spatial-temporal evolution of the lesioned cortex and its functional responses.This review provides a condensed conceptual review of the state of the art of this field, from models and magnetic resonance imaging techniques through to stem cell therapies.

View Article: PubMed Central - PubMed

Affiliation: Cerebrovascular Diseases Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta" , Milan , Italy.

ABSTRACT
Stroke continues to be a significant cause of death and disability worldwide. Although major advances have been made in the past decades in prevention, treatment, and rehabilitation, enormous challenges remain in the way of translating new therapeutic approaches from bench to bedside. Thrombolysis, while routinely used for ischemic stroke, is only a viable option within a narrow time window. Recently, progress in stem cell biology has opened up avenues to therapeutic strategies aimed at supporting and replacing neural cells in infarcted areas. Realistic experimental animal models are crucial to understand the mechanisms of neuronal survival following ischemic brain injury and to develop therapeutic interventions. Current studies on experimental stroke therapies evaluate the efficiency of neuroprotective agents and cell-based approaches using primarily rodent models of permanent or transient focal cerebral ischemia. In parallel, advancements in imaging techniques permit better mapping of the spatial-temporal evolution of the lesioned cortex and its functional responses. This review provides a condensed conceptual review of the state of the art of this field, from models and magnetic resonance imaging techniques through to stem cell therapies.

No MeSH data available.


Related in: MedlinePlus