Rat model of intracerebellar hemorrhage

Lekic, Tim; Tang, Jiping; Zhang, J. H.

doi:10.1007/978-3-211-09469-3_27

Cited by 17 publications

(19 citation statements)

References 11 publications

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“…Our preliminary report demonstrated the feasibility of collagenase-induced intra cerebellar hemorrhage (Lekic et al, 2008). We had used a modification of an established (basal ganglia) ICH model (Rosenberg et al, 1990) that circumvented the hematomal dissections outside rodent cerebella which had complicated autologous blood injection approaches in this brain region previously (Cossu et al, 1991; Cossu et al, 1994).…”

Section: Introductionmentioning

confidence: 72%

“…However, basal ganglia hemorrhage is a deep cerebral bleeding subtype, that as a group (basal ganglia, thalamus, and internal capsule), comprise no more than half of all cases (Flaherty et al, 2005), and animal models that represent the spectrum of ICH are highly needed (Gong et al, 2004; Song et al, 2007). Therefore this current study aimed to further establish a reproducible model of spontaneous cerebellar hemorrhage using stereotaxically injected collagenase (Lekic et al, 2008). This experimental paradigm could test therapeutic strategies for preventing the acutely devastating neurological deteriorations seen in patients (Jensen and St Louis, 2005; St Louis et al, 1998), and the application of cytoprotective interventions could further improve upon the lesion size and long-term neurological deficit of the survivors (Dolderer et al, 2004; Kelly et al, 2001; Okauchi et al, 2009; Strick et al, 2009; Thach, 1996).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the brain injury, neurobehavioral profiles, and histopathology in a rat model of cerebellar hemorrhage

Lekic

Rolland

Hartman

et al. 2011

Experimental Neurology

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Spontaneous cerebellar hemorrhage (SCH) represents approximately 10% of all intracerebral hemorrhage (ICH), and is an important clinical problem of which little is known. This study stereotaxically infused collagenase (type VII) into the deep cerebellar paramedian white matter, which corresponds to the most common clinical injury region. Measures of hemostasis (brain water, hemoglobin assay, Evans blue, collagen-IV, ZO-1, and MMP-2 and MMP-9) and neurodeficit were quantified twenty-four hours later (Experiment 1). Long-term functional outcomes were measured over thirty days using the ataxia scale (modified Luciani), open field, wire suspension, beam balance and inclined plane (Experiment 2). Neurocognitive ability was assessed on the third week using the rotarod (motor learning), T-maze (working memory) and water-maze (spatial learning and memory) (Experiment 3), followed by a histopathological analysis one week later (Experiment 4). Stereotaxic collagenase infusion caused dose-dependent elevations in brain edema, neurodeficit, hematoma volume and blood-brain barrier rupture, while physiological variables remained stable. Most functional outcomes normalized by third week, while neurocognitive testing showed deficits parallel to the cystic-cavitary lesion at thirty days. All animals survived until sacrifice, and obstructive hydrocephalus did not develop. These results suggest that the model can generate important translational information about this subtype of ICH, and could be used for future investigations of therapeutic mechanisms after cerebellar hemorrhage.

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Section: Introductionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Characterization of the brain injury, neurobehavioral profiles, and histopathology in a rat model of cerebellar hemorrhage

Lekic

Rolland

Hartman

et al. 2011

Experimental Neurology

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“…Most studies target the striatum but some have used the cerebellum (Lekic et al, 2008(Lekic et al, , 2011, motor cortex (Belayev et al, 2005;Xue and Del Bigio, 2000), or hippocampus (Song et al, 2007(Song et al, , 2008. The striatum is most often used, in part because it is a common site of ICH in patients, but also for convenience.…”

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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“…Due to the small size of the hindbrain region, previous attempts using autologous blood injection could not reproduce consistent hematomas, and consequently have received no further study [65–66]. Therefore our preliminary studies developed experimental models of infratentorial intracerebral hemorrhage (Figure 2) using clostridial collagenase to induce a hematoma in the cerebellum or brainstem [67–68]. These animal models successfully mimic the clinical hemorrhage at the infratentorial region (Figure 3).…”

Section: Experimental Studies: Hemorrhagic Strokementioning

confidence: 99%

Infratentorial Strokes for Posterior Circulation Folks: Clinical Correlations for Current Translational Therapeutics

Lekic

Krafft

Coats

et al. 2011

Transl. Stroke Res.

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Approximately 20 percent of all strokes will occur in the Infratentorial brain. This is within the vascular territory of the posterior vascular circulation. Very few clinical specifics are known about the therapeutic needs of this patient sub-population. Most evidence-based practices are founded from research about the treatment of anterior circulatory stroke. As a consequence, little is known about how stroke in the Infratentorial brain region would require a different approach. We characterized the neurovascular features of Infratentorial stroke, pathophysiological responses, and experimental models for further translational study.

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Rat model of intracerebellar hemorrhage

Cited by 17 publications

References 11 publications

Characterization of the brain injury, neurobehavioral profiles, and histopathology in a rat model of cerebellar hemorrhage

Characterization of the brain injury, neurobehavioral profiles, and histopathology in a rat model of cerebellar hemorrhage

A Critical Appraisal of Experimental Intracerebral Hemorrhage Research

Infratentorial Strokes for Posterior Circulation Folks: Clinical Correlations for Current Translational Therapeutics

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