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Cited by 54

The DOI matches its Crossref record; 97 of the 97 references it cites were found in a registry or an index.

Evolution of ischemic damage and behavioural deficit over 6 months after MCAo in the rat: selecting the optimal outcomes and statistical power for multi-centre preclinical trials.

Rewell, Sarah S. J., Churilov, Leonid, Sidon, T. Kate, Aleksoska, Elena, Cox, Susan F., Macleod, Malcolm R., Howells, David W.·2017·PLOS ONE
DOI 10.1371/journal.pone.0171688PMC PMC5300105
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Abstract

Key disparities between the timing and methods of assessment in animal stroke studies and clinical trial may be part of the reason for the failure to translate promising findings. This study investigates the development of ischemic damage after thread occlusion MCAo in the rat, using histological and behavioural outcomes. Using the adhesive removal test we investigate the longevity of behavioural deficit after ischemic stroke in rats, and examine the practicality of using such measures as the primary outcome for future studies. Ischemic stroke was induced in 132 Spontaneously Hypertensive Rats which were assessed for behavioural and histological deficits at 1, 3, 7, 14, 21, 28 days, 12 and 24 weeks (n>11 per timepoint). The basic behavioural score confirmed induction of stroke, with deficits specific to stroke animals. Within 7 days, these deficits resolved in 50% of animals. The adhesive removal test revealed contralateral neglect for up to 6 months following stroke. Sample size calculations to facilitate the use of this test as the primary experimental outcome resulted in cohort sizes much larger than are the norm for experimental studies. Histological damage progressed from a necrotic infarct to a hypercellular area that cleared to leave a fluid filled cavity. Whilst absolute volume of damage changed over time, when corrected for changes in hemispheric volume, an equivalent area of damage was lost at all timepoints. Using behavioural measures at chronic timepoints presents significant challenges to the basic science community in terms of the large number of animals required and the practicalities associated with this. Multicentre preclinical randomised controlled trials as advocated by the MultiPART consortium may be the only practical way to deal with this issue.

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Crossref · 10.1371/journal.pone.0171688

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Figures

Fig 1 Assessment of behavioural deficit for 6 months after stroke. Basic Behavioural Test: A) Forelimb flexion and torso twisting. B) Total score over the timecourse of the experiment. C) Presence of a deficit (shaded) over the course of the experiment. Adhesive Removal Test: D) Placement and removal of tape on the forepaws. E) Time to remove contralateral (left) tape relative to baseline ability. F) Time to remove ipsilateral tape relative to baseline ability. Sunflower Seed Challenge: G) Intact and broken seeds. H) Number of whole seeds remaining. I) Number of pieces of seed.
Fig 1 Assessment of behavioural deficit for 6 months after stroke. Basic Behavioural Test: A) Forelimb flexion and torso twisting. B) Total score over the timecourse of the experiment. C) Presence of a deficit (shaded) over the course of the experiment. Adhesive Removal Test: D) Placement and removal of tape on the forepaws. E) Time to remove contralateral (left) tape relative to baseline ability. F) Time to remove ipsilateral tape relative to baseline ability. Sunflower Seed Challenge: G) Intact and broken seeds. H) Number of whole seeds remaining. I) Number of pieces of seed.CC BY · PubMed Central
Fig 2 Ischemic damage over time after stroke. A) Total volume of damage including cavity (shaded). B) Changes in hemispheric size C) Ischemic damage corrected for the effect of oedema and atrophy. All values Mean±Standard Deviation. Animals are represented by individual data points. * p<0.05
Fig 2 Ischemic damage over time after stroke. A) Total volume of damage including cavity (shaded). B) Changes in hemispheric size C) Ischemic damage corrected for the effect of oedema and atrophy. All values Mean±Standard Deviation. Animals are represented by individual data points. * p<0.05CC BY · PubMed Central
Fig 3 Evolution of ischemic related damage resulting from MCAo. Representative images taken through the centre of the area of damage at approximately 1.7mm relative to bregma. A) Striatum. B) Cortex. Scale bar represents 50μm. Filled arrow head = red neuron; Open arrow head = hemorrhagic transformation; Arrow = Ghost neuron; Dotted line = striatal bundle; Star = Glial scar.
Fig 3 Evolution of ischemic related damage resulting from MCAo. Representative images taken through the centre of the area of damage at approximately 1.7mm relative to bregma. A) Striatum. B) Cortex. Scale bar represents 50μm. Filled arrow head = red neuron; Open arrow head = hemorrhagic transformation; Arrow = Ghost neuron; Dotted line = striatal bundle; Star = Glial scar.CC BY · PubMed Central

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Research works printed but not linked: 1

  1. PD Schellinger, 2012, Assessment of additional endpoints for trials in acute stroke—what, when, where, in who?, Int J Stroke, 7, 227, 10.1111/j.1747-4949.2012.00773.x · DOI

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Metadata

Authors
Rewell, S. S. J., Churilov, L., Sidon, T. K., Aleksoska, E., Cox, S. F., Macleod, M. R., & Howells, D. W.
ORCID
Rewell, Sarah S. J.
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-02-09
Volume
12
Issue
2
Pages
e0171688
ISSN
1932-6203
DOI
10.1371/journal.pone.0171688
PMC
PMC5300105
Cited by
54
References
97
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
National Health and Medical Research Council (GNT1013612)

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