Late changes in blood-brain barrier permeability in a rat tMCAO model of stroke detected by gadolinium-enhanced MRI

Morgan, C.A., Mesquita, M., Ashioti, M., Beech, J.S., Williams, S.C.R., Irving, E. and Cash, D. 2020. Late changes in blood-brain barrier permeability in a rat tMCAO model of stroke detected by gadolinium-enhanced MRI. Neurological Research. 42 (10), pp. 844-852. https://doi.org/10.1080/01616412.2020.1786637

TitleLate changes in blood-brain barrier permeability in a rat tMCAO model of stroke detected by gadolinium-enhanced MRI
TypeJournal article
AuthorsMorgan, C.A., Mesquita, M., Ashioti, M., Beech, J.S., Williams, S.C.R., Irving, E. and Cash, D.
Abstract

Objectives: After cerebral ischaemia the blood–brain barrier (BBB) may be compromised and this has been observed in both clinical and preclinical studies. The timing of BBB disruption after ischaemia has long been considered to be biphasic, however some groups contest this view. Therefore, the purpose of this study was to characterize the BBB permeability timecourse in a rat model at both acute and chronic time points.
Methods: Unilateral transient middle cerebral artery occlusion (tMCAO) was performed in 15 male Sprague Dawley rats. Change in T1-weighted MR signal before and after an injection of gadolinium-based contrast agent was calculated voxelwise to derive a BBB permeability index (BBBPI) at both early (6 h, 12 h, and 24 h) and late (7 and 14 days) time points.
Results: As expected, BBBPI in the non-lesioned ROI was not significantly different from pre-occlusion baseline at any time point. However, BBBPI in the ipsilateral (lesioned) ROI was statistically different to baseline at day 7 (p < 0.001) and day 14 (p < 0.01) post-tMCAO. There was a small, but not-significant increase in BBBPI in the earlier phase (at 6 hours).
Discussion: Our results indicate a significant late opening of the BBB. This is important as the majority of previous studies have only characterised an early acute BBB permeability in ischemia. However, the later period of increased permeability may indicate an optimal time for drug delivery across the BBB, when it is especially suited to drugs targeting delayed processes.

KeywordsStroke
transient middle cerebral artery occlusion
blood-brain barrier
chronic
MRI
contrast-enhanced
JournalNeurological Research
Journal citation42 (10), pp. 844-852
ISSN0161-6412
Year2020
PublisherTaylor & Francis
Digital Object Identifier (DOI)https://doi.org/10.1080/01616412.2020.1786637
PubMed ID32600164
Web address (URL)https://www.tandfonline.com/doi/full/10.1080/01616412.2020.1786637
Publication dates
Published online30 Jun 2020

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