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Animal models of ischemic stroke and their application in clinical research.

Fluri F, Schuhmann MK, Kleinschnitz C - Drug Des Devel Ther (2015)

Bottom Line: Furthermore, this model is characterized by reliable and well-reproducible infarcts.Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents.Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University Clinic Wuerzburg, Wuerzburg, Germany.

ABSTRACT
This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.

No MeSH data available.


Related in: MedlinePlus

Scheme of an intraluminal suture MCAo model and different methods for determining infarct volume.Notes: (A) Diagram of MCAo. (B) Representative of 2,3,5-triphenyl tetrazolium chloride staining of three consecutive coronal brain sections after transient MCAo. (C) Serial coronal T2-weighted gradient echo magnetic resonance images after transient MCAo. (D) Representative hematoxylin and eosin (top) and Nissl staining (bottom) of coronal brain sections after transient MCAo.Abbreviations: MCAo, middle cerebral artery occlusion; MCA, middle cerebral artery; ACA, anterior carotid artery; PCOM, posterior communicating artery; PPA, pterygopalatine artery; ECA, external carotid artery; CCA, common carotid artery.
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f1-dddt-9-3445: Scheme of an intraluminal suture MCAo model and different methods for determining infarct volume.Notes: (A) Diagram of MCAo. (B) Representative of 2,3,5-triphenyl tetrazolium chloride staining of three consecutive coronal brain sections after transient MCAo. (C) Serial coronal T2-weighted gradient echo magnetic resonance images after transient MCAo. (D) Representative hematoxylin and eosin (top) and Nissl staining (bottom) of coronal brain sections after transient MCAo.Abbreviations: MCAo, middle cerebral artery occlusion; MCA, middle cerebral artery; ACA, anterior carotid artery; PCOM, posterior communicating artery; PPA, pterygopalatine artery; ECA, external carotid artery; CCA, common carotid artery.

Mentions: Technically, the MCAo model is less invasive and does not require craniectomy and thus avoids damage to cranial structures. This technique involves temporarily occluding the common carotid artery (CCA), introducing a suture directly into the internal carotid artery (ICA), and advancing the suture until it interrupts the blood supply to the MCA (Figure 1). In a modified manner, the suture is inserted into the transected external carotid artery (ECA), using the ECA trunk as a path to advance a suture through the ICA. Laser Doppler flowmetry can be a useful tool for ensuring complete MCAo.21 This method enables permanent MCAo or transient ischemia with reperfusion. The ECA approach is a better choice for transient MCAo because it maintains the anatomic integrity that is required for reperfusion.22


Animal models of ischemic stroke and their application in clinical research.

Fluri F, Schuhmann MK, Kleinschnitz C - Drug Des Devel Ther (2015)

Scheme of an intraluminal suture MCAo model and different methods for determining infarct volume.Notes: (A) Diagram of MCAo. (B) Representative of 2,3,5-triphenyl tetrazolium chloride staining of three consecutive coronal brain sections after transient MCAo. (C) Serial coronal T2-weighted gradient echo magnetic resonance images after transient MCAo. (D) Representative hematoxylin and eosin (top) and Nissl staining (bottom) of coronal brain sections after transient MCAo.Abbreviations: MCAo, middle cerebral artery occlusion; MCA, middle cerebral artery; ACA, anterior carotid artery; PCOM, posterior communicating artery; PPA, pterygopalatine artery; ECA, external carotid artery; CCA, common carotid artery.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494187&req=5

f1-dddt-9-3445: Scheme of an intraluminal suture MCAo model and different methods for determining infarct volume.Notes: (A) Diagram of MCAo. (B) Representative of 2,3,5-triphenyl tetrazolium chloride staining of three consecutive coronal brain sections after transient MCAo. (C) Serial coronal T2-weighted gradient echo magnetic resonance images after transient MCAo. (D) Representative hematoxylin and eosin (top) and Nissl staining (bottom) of coronal brain sections after transient MCAo.Abbreviations: MCAo, middle cerebral artery occlusion; MCA, middle cerebral artery; ACA, anterior carotid artery; PCOM, posterior communicating artery; PPA, pterygopalatine artery; ECA, external carotid artery; CCA, common carotid artery.
Mentions: Technically, the MCAo model is less invasive and does not require craniectomy and thus avoids damage to cranial structures. This technique involves temporarily occluding the common carotid artery (CCA), introducing a suture directly into the internal carotid artery (ICA), and advancing the suture until it interrupts the blood supply to the MCA (Figure 1). In a modified manner, the suture is inserted into the transected external carotid artery (ECA), using the ECA trunk as a path to advance a suture through the ICA. Laser Doppler flowmetry can be a useful tool for ensuring complete MCAo.21 This method enables permanent MCAo or transient ischemia with reperfusion. The ECA approach is a better choice for transient MCAo because it maintains the anatomic integrity that is required for reperfusion.22

Bottom Line: Furthermore, this model is characterized by reliable and well-reproducible infarcts.Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents.Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University Clinic Wuerzburg, Wuerzburg, Germany.

ABSTRACT
This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.

No MeSH data available.


Related in: MedlinePlus