Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage

Boltze, Johannes; Ferrara, Fabienne; Hainsworth, Atticus H.; Bridges, Leslie; Zille, Marietta; Lobsien, Donald; Barthel, Henryk; McLeod, Damian D.; Gräßer, Felix; Pietsch, Sören; Schatzl, Ann-Kathrin; Dreyer, Antje; Nitzsche, Björn

doi:10.1177/0271678x18802119

Cited by 17 publications

(19 citation statements)

References 46 publications

(62 reference statements)

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“…The data were tested for normality and an independent t -test performed to determine significant differences between hemispheres using the statistical software SPSS (significance considered present with a p -value < 0.05). Laterality indices were calculated according to the following formula from Boltze et al (2018):…”

Section: Methodsmentioning

confidence: 99%

Equine Stereotaxtic Population Average Brain Atlas With Neuroanatomic Correlation

et al. 2019

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There is growing interest in the horse for behavioral, neuroanatomic and neuroscientific research due to its large and complex brain, cognitive abilities and long lifespan making it neurologically interesting and a potential large animal model for several neuropsychological diseases. Magnetic resonance imaging (MRI) is a powerful neuroscientific research tool that can be performed in vivo, with adapted equine facilities, or ex-vivo in the research setting. The brain atlas is a fundamental resource for neuroimaging research, and have been created for a multitude animal models, however, none currently exist for the equine brain. In this study, we document the creation of a high-resolution stereotaxic population average brain atlas of the equine. The atlas was generated from nine unfixed equine cadaver brains imaged within 4 h of euthanasia in a 3-tesla MRI. The atlas was generated using linear and non-linear registration methods and quality assessed using signal and contrast to noise calculations. Tissue segmentation maps (TSMs) for white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF), were generated and manually segmented anatomic priors created for multiple subcortical brain structures. The resulting atlas was validated and correlated to gross anatomical specimens and is made freely available at as an online resource for researchers (https://doi.org/10.7298/cyrs-7b51.2). The mean volume metrics for the whole brain, GM and WM for the included subjects were documented and the effect of age and laterality assessed. Alterations in brain volume in relation to age were identified, though these variables were not found to be significantly correlated. All subjects had higher whole brain, GM and WM volumes on the right side, consistent with the well documented right forebrain dominance of horses. This atlas provides an important tool for automated processing in equine and translational neuroimaging research.

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Section: Methodsmentioning

confidence: 99%

Equine Stereotaxtic Population Average Brain Atlas With Neuroanatomic Correlation

et al. 2019

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Section: Larger Mammalian Modelsmentioning

confidence: 66%

“…Boltze and colleagues [ 113 ] recently replicated the autologous blood model in adult sheep, observing similar histopathological observations as found in rodent models, such as brain resident cell recruitment and axonal damage. Whilst this preliminary study was used to demonstrate how ovine models can be used as a successful pre-clinical model of ICH, in the future, it is hoped that they will provide additional translational benefits when studying surgical interventions, for example like those performed in the MISTIE and STITCH trials [ 113 – 118 ]. Such candidate intervention techniques are infrequently implemented in other pre-clinical models, and due to the small size of brain and skull, it may be more desirable to perform these types of surgical intervention techniques in an animal model with a larger head [ 37 , 119 , 120 ].…”

Section: Larger Mammalian Modelsmentioning

confidence: 66%

A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research

Withers

Parry‐Jones

Allan

et al. 2020

Transl. Stroke Res.

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Apart from acute and chronic blood pressure lowering, we have no specific medications to prevent intracerebral haemorrhage (ICH) or improve outcomes once bleeding has occurred. One reason for this may be related to particular limitations associated with the current pre-clinical models of ICH, leading to a failure to translate into the clinic. It would seem that a breakdown in the ‘drug development pipeline’ currently exists for translational ICH research which needs to be urgently addressed. Here, we review the most commonly used pre-clinical models of ICH and discuss their advantages and disadvantages in the context of translational studies. We propose that to increase our chances of successfully identifying new therapeutics for ICH, a bi-directional, 2- or 3-pronged approach using more than one model species/system could be useful for confirming key pre-clinical observations. Furthermore, we highlight that post-mortem/ex-vivo ICH patient material is a precious and underused resource which could play an essential role in the verification of experimental results prior to consideration for further clinical investigation. Embracing multidisciplinary collaboration between pre-clinical and clinical ICH research groups will be essential to ensure the success of this type of approach in the future.

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“…34 Finally, we did not include a number of insightful imaging studies because they did not conduct a formal inter-group comparison. 35,36,37,38…”

Section: Discussionmentioning

confidence: 99%

Quality and validity of large animal experiments in stroke: A systematic review

Kringe

Sena

Motschall

et al. 2020

J Cereb Blood Flow Metab

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An important factor for successful translational stroke research is study quality. Low-quality studies are at risk of biased results and effect overestimation, as has been intensely discussed for small animal stroke research. However, little is known about the methodological rigor and quality in large animal stroke models, which are becoming more frequently used in the field. Based on research in two databases, this systematic review surveys and analyses the methodological quality in large animal stroke research. Quality analysis was based on the Stroke Therapy Academic Industry Roundtable and the Animals in Research: Reporting In Vivo Experiments guidelines. Our analysis revealed that large animal models are utilized with similar shortcomings as small animal models. Moreover, translational benefits of large animal models may be limited due to lacking implementation of important quality criteria such as randomization, allocation concealment, and blinded assessment of outcome. On the other hand, an increase of study quality over time and a positive correlation between study quality and journal impact factor were identified. Based on the obtained findings, we derive recommendations for optimal study planning, conducting, and data analysis/reporting when using large animal stroke models to fully benefit from the translational advantages offered by these models.

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Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage

Cited by 17 publications

References 46 publications

Equine Stereotaxtic Population Average Brain Atlas With Neuroanatomic Correlation

Equine Stereotaxtic Population Average Brain Atlas With Neuroanatomic Correlation

A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research

Quality and validity of large animal experiments in stroke: A systematic review

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