Experimental intracerebral hemorrhage: Description of a double injection model in rats

Deinsberger, Wolfgang; Vogel, Johannes; Kuschinsky, Wolgang; Auer, L. M.; Böker, Dieter-Karsten

doi:10.1080/01616412.1996.11740456

Cited by 93 publications

(44 citation statements)

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“…Larger hematomas, whether from injected blood or collagenase infusion, can also damage thalamus and globus pallidus. Backflow can be reduced with the 'double-injection' method (Belayev et al, 2003;Deinsberger et al, 1996) where the bulk of the blood is infused after an initial bolus is allowed to clot. Due to these potential problems, we strongly recommend publishing photomicrographs showing brain injury, a practice that is not routinely done in the ICH field.…”

Section: Surgical Approachmentioning

confidence: 99%

A Critical Appraisal of Experimental Intracerebral Hemorrhage Research

MacLellan

Paquette

Colbourne

2012

J Cereb Blood Flow Metab

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The likelihood of translating therapeutic interventions for stroke rests on the quality of preclinical science. Given the limited success of putative treatments for ischemic stroke and the reasons put forth to explain it, we sought to determine whether such problems hamper progress for intracerebral hemorrhage (ICH). Approximately 10% to 20% of strokes result from an ICH, which results in considerable disability and high mortality. Several animal models reproduce ICH and its underlying pathophysiology, and these models have been widely used to evaluate treatments. As yet, however, none has successfully translated. In this review, we focus on rodent models of ICH, highlighting differences among them (e.g., pathophysiology), issues with experimental design and analysis, and choice of end points. A Pub Med search for experimental ICH (years: 2007 to 31 July 2011) found 121 papers. Of these, 84% tested neuroprotectants, 11% tested stem cell therapies, and 5% tested rehabilitation therapies. We reviewed these to examine study quality (e.g., use of blinding procedures) and choice of end points (e.g., behavioral testing). Not surprisingly, the problems that have plagued the ischemia field are also prevalent in ICH literature. Based on these data, several recommendations are put forth to facilitate progress in identifying effective treatments for ICH.

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Section: Surgical Approachmentioning

confidence: 99%

A Critical Appraisal of Experimental Intracerebral Hemorrhage Research

MacLellan

Paquette

Colbourne

2012

J Cereb Blood Flow Metab

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“…Double injection, where slow infusion of a small blood volume into the striatum allows blood clotting along the needle track, followed by the remaining blood to generate the hematoma, results in reproducible hematoma volumes (Deinsberger et al, 1996). In addition, the autologous blood injection model produces a consistent neurologic deficit, brain swelling, and cortical hypoperfusion (Belayev et al, 2003).…”

Section: Autologous Blood Modelmentioning

confidence: 99%

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Kirkman

Allan

Parry‐Jones

2011

J Cereb Blood Flow Metab

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Intracerebral hemorrhage (ICH) has the highest mortality of all stroke subtypes, yet treatments are mainly limited to supportive management, and surgery remains controversial. Despite significant advances in our understanding of ICH pathophysiology, we still lack preclinical models that accurately replicate the underlying mechanisms of injury. Current experimental ICH models (including autologous blood and collagenase injection) simulate different aspects of ICH-mediated injury but lack some features of the clinical condition. Newly developed models, notably hypertension-and oral anticoagulant therapy-associated ICH models, offer added benefits but further study is needed to fully validate them. Here, we describe and discuss current approaches to experimental ICH, with suggestions for changes in how this condition is studied in the laboratory. Although advances in imaging over the past few decades have allowed greater insight into clinical ICH, there remains an important role for experimental models in furthering our understanding of the basic pathophysiologic processes underlying ICH, provided limitations of animal models are borne in mind. Owing to differences in existing models and the failed translation of benefits in experimental ICH to clinical practice, putative neuroprotectants should be trialed in multiple models using both histological and functional outcomes until a more accurate model of ICH is developed.

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“…8,9 The mouse was placed in a stereotactic frame (David Kopf Instruments). A 30-gauge stainless steel cannula was introduced through a burr hole into the left striatum (2 mm lateral to midline, 1 mm anterior to bregma, depth 4 mm below the surface of the skull).…”

Section: Model Of Ichmentioning

confidence: 99%

“…7 Recently, a doubleinjection ICH model in the rat has been developed in which a small amount of blood is infused into the striatum at a slow rate to allow blood clotting along the needle track; the remaining blood is then infused to generate the hematoma. 8,9 This method creates a reproducible hematoma volume suitable for study of the pathophysiology and treatment of ICH. 9,10 The present study was conducted to validate a modified double-injection method in the mouse and to assess cerebral blood flow (CBF), neurological score, hematoma volume, and brain swelling.…”

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confidence: 99%

Experimental Intracerebral Hemorrhage in the Mouse

Belayev

Saul

Curbelo

et al. 2003

Stroke

108

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Background and Purpose-A major limitation of intracerebral hemorrhage (ICH) research is the lack of reproducible animal models. The present study was conducted to validate in the mouse the double-injection method of ICH initially developed in the rat. We investigated the effect of intrastriatal injection of blood or cerebrospinal fluid (CSF) on cerebral blood flow (CBF), neurological score, hematoma volume, and brain swelling. Methods-Male C57BL/6 mice were anesthetized with halothane/nitrous oxide delivered by face mask. Rectal and cranial temperatures were regulated at 37°C to 37.5°C. Mice were placed in a stereotactic frame, and a 30-gauge stainless steel cannula was introduced through a burr hole into the left striatum. Each mouse received a 5-L injection of either whole blood or CSF (over 3 minutes), followed 7 minutes later by 10 L injected over 5 minutes. The injection cannula was slowly withdrawn 10 minutes after the second injection. Control mice had only cannula insertion. CBF was studied by laser Doppler perfusion imaging. Neurological status was evaluated on days 1 and 2. After 2 days, hematoma volume and brain swelling were calculated. Results-Physiological values were stable. Mice with ICH but not those with CSF or cannula alone had a marked, persistent neurological deficit and a highly reproducible hematoma, whose meanϮSEM volume was 2.0Ϯ0.2 mm

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Experimental intracerebral hemorrhage: Description of a double injection model in rats

Cited by 93 publications

References 0 publications

A Critical Appraisal of Experimental Intracerebral Hemorrhage Research

A Critical Appraisal of Experimental Intracerebral Hemorrhage Research

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Experimental Intracerebral Hemorrhage in the Mouse

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