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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

Temporal evolution of cerebral blood flow (CBF) changes for untreated (A) and recombinant tissue plasminogen activator (rt-PA)-treated (B) rats after embolization. Reproduced from Ref. (106) by permission of Lippincott-Raven Publishers Inc/Nature Publishing Group.
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Figure 3: Temporal evolution of cerebral blood flow (CBF) changes for untreated (A) and recombinant tissue plasminogen activator (rt-PA)-treated (B) rats after embolization. Reproduced from Ref. (106) by permission of Lippincott-Raven Publishers Inc/Nature Publishing Group.

Mentions: Unfortunately, mainly due to scanning time limitations, many research groups in the past have used only DWI or PWI alone for assessing therapeutic response in experimental models. However, those that do have obtained results clearly demonstrate the value of combining these techniques. For instance, Jiang et al. have demonstrated that rapid recanalization by means of rt-PA of embolically occluded brain arteries leads to increased rCBF and ADC which foreruns reduced lesion volume (106) (Figure 3). In another study, Meng et al. using DWI/PWI mismatch in a MCAO model demonstrated a reduction of volume of the infarcted lesion due to a mechanical reperfusion at 60 min after ischemia onset (107).


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 evolution of cerebral blood flow (CBF) changes for untreated (A) and recombinant tissue plasminogen activator (rt-PA)-treated (B) rats after embolization. Reproduced from Ref. (106) by permission of Lippincott-Raven Publishers Inc/Nature Publishing Group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Temporal evolution of cerebral blood flow (CBF) changes for untreated (A) and recombinant tissue plasminogen activator (rt-PA)-treated (B) rats after embolization. Reproduced from Ref. (106) by permission of Lippincott-Raven Publishers Inc/Nature Publishing Group.
Mentions: Unfortunately, mainly due to scanning time limitations, many research groups in the past have used only DWI or PWI alone for assessing therapeutic response in experimental models. However, those that do have obtained results clearly demonstrate the value of combining these techniques. For instance, Jiang et al. have demonstrated that rapid recanalization by means of rt-PA of embolically occluded brain arteries leads to increased rCBF and ADC which foreruns reduced lesion volume (106) (Figure 3). In another study, Meng et al. using DWI/PWI mismatch in a MCAO model demonstrated a reduction of volume of the infarcted lesion due to a mechanical reperfusion at 60 min after ischemia onset (107).

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