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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

Diffusivity and T2 maps demonstrating the consequences of transient left MCAO in the rat. Time-courses of diffusion (ADC) and T2 contrast changes. Early ADC pseudo-normalization is followed by a further reduction, until eventually the ADC is significantly elevated with respect to tissue in the contralateral hemisphere and the two maps appear similar. Reproduced from Ref. (139) by permission of Wiley-Liss/John Wiley & Sons Inc.
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Figure 2: Diffusivity and T2 maps demonstrating the consequences of transient left MCAO in the rat. Time-courses of diffusion (ADC) and T2 contrast changes. Early ADC pseudo-normalization is followed by a further reduction, until eventually the ADC is significantly elevated with respect to tissue in the contralateral hemisphere and the two maps appear similar. Reproduced from Ref. (139) by permission of Wiley-Liss/John Wiley & Sons Inc.

Mentions: Diffusion-weighted imaging reveals strong image contrast changes within minutes following the onset of acute cerebral ischemia and additionally allows the follow-up of tissue changes through the subacute and chronic phases (92, 93). During ischemic stroke, the apparent diffusion coefficient (ADC) follows a “U-shape” time-course, characterized by a rapid initial decrease, as early as 20 min after the onset of the ischemia (94, 95): intracellular water accumulation, due to rapid failure of high-energy metabolism and associated ionic pumps, leads to cellular swelling (cytotoxic edema) and consequent narrowing of the extracellular matrix volume (96). This is a robust effect that is consistently observed in experimental models (Figure 2) and patient studies. After 3–5 days, the ADC in the irreversibly infarcted area begins to increase, due to cell lysis and development of vasogenic edema; after a period of “pseudo-normalization” of ADC values, the lesioned area stabilizes on high diffusivity values. In particular, in acute phase ADC maps, when combined with perfusion measurements, allow to distinguish the core region from the penumbra, with ADC gradually decreased from the periphery to the center of the ischemic region (97–99).


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)

Diffusivity and T2 maps demonstrating the consequences of transient left MCAO in the rat. Time-courses of diffusion (ADC) and T2 contrast changes. Early ADC pseudo-normalization is followed by a further reduction, until eventually the ADC is significantly elevated with respect to tissue in the contralateral hemisphere and the two maps appear similar. Reproduced from Ref. (139) by permission of Wiley-Liss/John Wiley & Sons Inc.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Diffusivity and T2 maps demonstrating the consequences of transient left MCAO in the rat. Time-courses of diffusion (ADC) and T2 contrast changes. Early ADC pseudo-normalization is followed by a further reduction, until eventually the ADC is significantly elevated with respect to tissue in the contralateral hemisphere and the two maps appear similar. Reproduced from Ref. (139) by permission of Wiley-Liss/John Wiley & Sons Inc.
Mentions: Diffusion-weighted imaging reveals strong image contrast changes within minutes following the onset of acute cerebral ischemia and additionally allows the follow-up of tissue changes through the subacute and chronic phases (92, 93). During ischemic stroke, the apparent diffusion coefficient (ADC) follows a “U-shape” time-course, characterized by a rapid initial decrease, as early as 20 min after the onset of the ischemia (94, 95): intracellular water accumulation, due to rapid failure of high-energy metabolism and associated ionic pumps, leads to cellular swelling (cytotoxic edema) and consequent narrowing of the extracellular matrix volume (96). This is a robust effect that is consistently observed in experimental models (Figure 2) and patient studies. After 3–5 days, the ADC in the irreversibly infarcted area begins to increase, due to cell lysis and development of vasogenic edema; after a period of “pseudo-normalization” of ADC values, the lesioned area stabilizes on high diffusivity values. In particular, in acute phase ADC maps, when combined with perfusion measurements, allow to distinguish the core region from the penumbra, with ADC gradually decreased from the periphery to the center of the ischemic region (97–99).

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