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dc.contributor.authorRewell, SSJ
dc.contributor.authorChurilov, L
dc.contributor.authorSidon, TK
dc.contributor.authorAleksoska, E
dc.contributor.authorCox, SF
dc.contributor.authorMacleod, MR
dc.contributor.authorHowells, DW
dc.date.accessioned2020-12-22T04:46:30Z
dc.date.available2020-12-22T04:46:30Z
dc.date.issued2017-02-09
dc.identifierpii: PONE-D-16-49125
dc.identifier.citationRewell, S. S. J., Churilov, L., Sidon, T. K., Aleksoska, E., Cox, S. F., Macleod, M. R. & Howells, D. W. (2017). 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), https://doi.org/10.1371/journal.pone.0171688.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/258138
dc.description.abstractKey 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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEvolution 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
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0171688
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.affiliation.departmentClinical School (Austin Health)
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS One
melbourne.source.volume12
melbourne.source.issue2
dc.rights.licenseCC BY
melbourne.elementsid1187114
melbourne.contributor.authorRewell, Sarah
melbourne.contributor.authorChurilov, Leonid
melbourne.contributor.authorHowells, David
melbourne.contributor.authorAleksoska, Elena
melbourne.contributor.authorSidon, Tara
melbourne.contributor.authorCox, Susan
melbourne.contributor.authorMACLEOD, MALCOLM
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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