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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
Citation
Rewell, SSJ and Churilov, L and Sidon, TK and Aleksoska, E and Cox, SF and Macleod, MR and Howells, DW, 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, PLoS ONE, 12, (2) Article 0171688. ISSN 1932-6203 (2017) [Refereed Article]
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Copyright Statement
Copyright: © 2017 Rewell et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
DOI: doi:10.1371/journal.pone.0171688
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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Neurosciences |
| Research Field: | Neurology and neuromuscular diseases |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Diagnosis of human diseases and conditions |
| UTAS Author: | Howells, DW (Professor David Howells) |
| ID Code: | 151607 |
| Year Published: | 2017 |
| Web of Science® Times Cited: | 38 |
| Deposited By: | Medicine |
| Deposited On: | 2022-08-02 |
| Last Modified: | 2022-12-06 |
| Downloads: | 2 View Download Statistics |
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