Limits...
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

Temporal changes of functional activation elicited by forepaw electrical stimulation over 6 months. Rats treated with stem cells (bottom) demonstrated more rapid and marked “renormalization” of the activation pattern in comparison to controls (top). Reproduced from Ref. (114) by permission of the authors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928567&req=5

Figure 4: Temporal changes of functional activation elicited by forepaw electrical stimulation over 6 months. Rats treated with stem cells (bottom) demonstrated more rapid and marked “renormalization” of the activation pattern in comparison to controls (top). Reproduced from Ref. (114) by permission of the authors.

Mentions: The complexity of these response patterns implies that there is no straightforward answer as to whether increased or decreased activity in a given region is a sign of functional recovery. Some studies have demonstrated that functional recovery is mainly associated with activation patterns that resemble as closely as possible those obtained prior to lesion onset (113) and that successful reparative therapies enhance this pattern of functional recovery (114) (Figure 4). For interpreting the nature of specific effects, correlation with behavioral scores is essential, to distinguish between loss of inhibition and functional specificity from genuine plasticity supporting functional recovery (115, 116). There are two main problems implementing fMRI in animal models. The first is anesthesia, which by definition suppresses central nervous system activity and for which there may be a very narrow dose margin available, implying that the dose cannot be lowered enough to obtain reliable fMRI responses without also incurring into movement artifacts. The other problem is that the hemodynamic response at the basis of fMRI can be impaired for countless reasons that are not related to neuronal function, such as impaired cerebrovascular reactivity. For this reason fMRI is frequently performed in conjunction with evoked potentials, which do not provide good spatial information but, on the other hand, represent neuroelectric activity directly and may therefore detect situations where neural activity is preserved but rendered invisible to fMRI through physiological confounds (116).


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)

Temporal changes of functional activation elicited by forepaw electrical stimulation over 6 months. Rats treated with stem cells (bottom) demonstrated more rapid and marked “renormalization” of the activation pattern in comparison to controls (top). Reproduced from Ref. (114) by permission of the authors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Temporal changes of functional activation elicited by forepaw electrical stimulation over 6 months. Rats treated with stem cells (bottom) demonstrated more rapid and marked “renormalization” of the activation pattern in comparison to controls (top). Reproduced from Ref. (114) by permission of the authors.
Mentions: The complexity of these response patterns implies that there is no straightforward answer as to whether increased or decreased activity in a given region is a sign of functional recovery. Some studies have demonstrated that functional recovery is mainly associated with activation patterns that resemble as closely as possible those obtained prior to lesion onset (113) and that successful reparative therapies enhance this pattern of functional recovery (114) (Figure 4). For interpreting the nature of specific effects, correlation with behavioral scores is essential, to distinguish between loss of inhibition and functional specificity from genuine plasticity supporting functional recovery (115, 116). There are two main problems implementing fMRI in animal models. The first is anesthesia, which by definition suppresses central nervous system activity and for which there may be a very narrow dose margin available, implying that the dose cannot be lowered enough to obtain reliable fMRI responses without also incurring into movement artifacts. The other problem is that the hemodynamic response at the basis of fMRI can be impaired for countless reasons that are not related to neuronal function, such as impaired cerebrovascular reactivity. For this reason fMRI is frequently performed in conjunction with evoked potentials, which do not provide good spatial information but, on the other hand, represent neuroelectric activity directly and may therefore detect situations where neural activity is preserved but rendered invisible to fMRI through physiological confounds (116).

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