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Translating basic science research to clinical application: models and strategies for intracerebral hemorrhage.

Leonardo CC, Robbins S, Doré S - Front Neurol (2012)

Bottom Line: While the need for novel therapeutics is clear, it is also critical that diagnostics be improved to allow for more rapid treatment upon hospital admission.Several preclinical models of ICH have been developed and are widely used to recapitulate human pathology.Because each model has limitations, the burden lies with the investigator to clearly define the question being asked and select the model system that is most relevant to that question.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease, University of Florida Gainesville, FL, USA.

ABSTRACT
Preclinical stroke models provide insights into mechanisms of cellular injury and potential therapeutic targets. Renewed efforts to standardize preclinical practices and adopt more rigorous approaches reflect the assumption that a better class of compounds will translate into clinical efficacy. While the need for novel therapeutics is clear, it is also critical that diagnostics be improved to allow for more rapid treatment upon hospital admission. Advances in imaging techniques have aided in the diagnosis of stroke, yet current limitations and expenses demonstrate the need for new and complementary approaches. Intracerebral hemorrhage (ICH) exhibits the highest mortality rate, displays unique pathology and requires specialized treatment strategies relative to other forms of stroke. The aggressive nature and severe consequences of ICH underscore the need for novel therapeutic approaches as well as accurate and expeditious diagnostic tools. The use of experimental models will continue to aid in addressing these important issues as the field attempts to translate basic science findings into the clinical setting. Several preclinical models of ICH have been developed and are widely used to recapitulate human pathology. Because each model has limitations, the burden lies with the investigator to clearly define the question being asked and select the model system that is most relevant to that question. It may also be necessary to optimize and refine pre-existing paradigms, or generate new paradigms, as the future success of translational research is dependent upon the ability to mimic human sequelae and assess clinically relevant outcome measures as means to evaluate therapeutic efficacy.

No MeSH data available.


Related in: MedlinePlus

Schematic depicts models commonly used to mimic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Autologous blood injection involves single- or double injection of autologous blood, or blood fractions, to generate a hematoma within the brain parenchyma. Collagenase injection is accomplished through the injection of recombinant bacterial collagenase to mimic blood extravasation following the rupture of cerebral arterial vasculature. Striatal balloon inflation is utilized to assess the mass hematoma effect on cellular injury and to evaluate the consequences of hematoma removal. Models of SAH produce blood accumulation in the subarachnoid space either by injection into the cistern magna or perforation of the anterior cerebral artery. Arrows represent injection route and demarcate the mass hematoma region.
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Figure 1: Schematic depicts models commonly used to mimic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Autologous blood injection involves single- or double injection of autologous blood, or blood fractions, to generate a hematoma within the brain parenchyma. Collagenase injection is accomplished through the injection of recombinant bacterial collagenase to mimic blood extravasation following the rupture of cerebral arterial vasculature. Striatal balloon inflation is utilized to assess the mass hematoma effect on cellular injury and to evaluate the consequences of hematoma removal. Models of SAH produce blood accumulation in the subarachnoid space either by injection into the cistern magna or perforation of the anterior cerebral artery. Arrows represent injection route and demarcate the mass hematoma region.

Mentions: The use of animal models has been of great benefit for identifying mechanisms of injury and novel therapeutics. In recent years, however, the failure of candidate therapeutics in clinical stroke trials has placed additional pressure on basic scientists to develop better preclinical models that more closely mimic human conditions. There are several well-accepted models that are commonly utilized to recapitulate hemorrhagic stroke (Figure 1). Although there is no perfect model, each is effective in reproducing certain aspects of the clinical pathology (Table 1). What follows is a detailed comparison of the various preclinical models, with special attention afforded to those aspects which relate to translating findings to the clinical setting.


Translating basic science research to clinical application: models and strategies for intracerebral hemorrhage.

Leonardo CC, Robbins S, Doré S - Front Neurol (2012)

Schematic depicts models commonly used to mimic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Autologous blood injection involves single- or double injection of autologous blood, or blood fractions, to generate a hematoma within the brain parenchyma. Collagenase injection is accomplished through the injection of recombinant bacterial collagenase to mimic blood extravasation following the rupture of cerebral arterial vasculature. Striatal balloon inflation is utilized to assess the mass hematoma effect on cellular injury and to evaluate the consequences of hematoma removal. Models of SAH produce blood accumulation in the subarachnoid space either by injection into the cistern magna or perforation of the anterior cerebral artery. Arrows represent injection route and demarcate the mass hematoma region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3361857&req=5

Figure 1: Schematic depicts models commonly used to mimic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Autologous blood injection involves single- or double injection of autologous blood, or blood fractions, to generate a hematoma within the brain parenchyma. Collagenase injection is accomplished through the injection of recombinant bacterial collagenase to mimic blood extravasation following the rupture of cerebral arterial vasculature. Striatal balloon inflation is utilized to assess the mass hematoma effect on cellular injury and to evaluate the consequences of hematoma removal. Models of SAH produce blood accumulation in the subarachnoid space either by injection into the cistern magna or perforation of the anterior cerebral artery. Arrows represent injection route and demarcate the mass hematoma region.
Mentions: The use of animal models has been of great benefit for identifying mechanisms of injury and novel therapeutics. In recent years, however, the failure of candidate therapeutics in clinical stroke trials has placed additional pressure on basic scientists to develop better preclinical models that more closely mimic human conditions. There are several well-accepted models that are commonly utilized to recapitulate hemorrhagic stroke (Figure 1). Although there is no perfect model, each is effective in reproducing certain aspects of the clinical pathology (Table 1). What follows is a detailed comparison of the various preclinical models, with special attention afforded to those aspects which relate to translating findings to the clinical setting.

Bottom Line: While the need for novel therapeutics is clear, it is also critical that diagnostics be improved to allow for more rapid treatment upon hospital admission.Several preclinical models of ICH have been developed and are widely used to recapitulate human pathology.Because each model has limitations, the burden lies with the investigator to clearly define the question being asked and select the model system that is most relevant to that question.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease, University of Florida Gainesville, FL, USA.

ABSTRACT
Preclinical stroke models provide insights into mechanisms of cellular injury and potential therapeutic targets. Renewed efforts to standardize preclinical practices and adopt more rigorous approaches reflect the assumption that a better class of compounds will translate into clinical efficacy. While the need for novel therapeutics is clear, it is also critical that diagnostics be improved to allow for more rapid treatment upon hospital admission. Advances in imaging techniques have aided in the diagnosis of stroke, yet current limitations and expenses demonstrate the need for new and complementary approaches. Intracerebral hemorrhage (ICH) exhibits the highest mortality rate, displays unique pathology and requires specialized treatment strategies relative to other forms of stroke. The aggressive nature and severe consequences of ICH underscore the need for novel therapeutic approaches as well as accurate and expeditious diagnostic tools. The use of experimental models will continue to aid in addressing these important issues as the field attempts to translate basic science findings into the clinical setting. Several preclinical models of ICH have been developed and are widely used to recapitulate human pathology. Because each model has limitations, the burden lies with the investigator to clearly define the question being asked and select the model system that is most relevant to that question. It may also be necessary to optimize and refine pre-existing paradigms, or generate new paradigms, as the future success of translational research is dependent upon the ability to mimic human sequelae and assess clinically relevant outcome measures as means to evaluate therapeutic efficacy.

No MeSH data available.


Related in: MedlinePlus