Exploring the long-term blood-brain-barrier alterations associated with post-stroke secondary neurodegeneration in an ovine model. — The Association Specialists
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Exploring the long-term blood-brain-barrier alterations associated with post-stroke secondary neurodegeneration in an ovine model. (21498)

Rosie A Costigan-Dwyer 1 , Shannon M Stuckey 1 , Rebecca J Hood 1 , Samantha L Joubert 1 , Tracy D Farr 2 , Mustafa Almuqbel 3 , Georgia Williams 4 , Mark Jenkinson 5 6 , Renee J Turner 1
  1. University of Adelaide, Adelaide, SA, Australia
  2. School of Life Sciences , The University of Nottigham, Nottigham, United Kingdom
  3. Department of Medical Radiography, University of Doha for Science and Technology, Doha, Qatar
  4. Preclinical, Imaging & Research Laboratories, South Australian Health and Medical Research Institute, Adelaide, Australia
  5. School of Computer and Mathematical Sciences, Australian Institute for Machine Learning, Adelaide, Australia
  6. Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom

Background: >70% of stroke survivors experience long-term cognitive impairments, which has been linked to secondary neurodegeneration (SND). SND involves the progressive death of neurons in regions distal to the stroke site i.e., thalamus and hippocampus. Within these regions blood-brain-barrier (BBB) dysfunction has been observed out to 3-months with links to cognitive decline, however long-term investigations remain scarce.

Aim: This study sought to explore the spatio-temporal profile of chronic BBB permeability at SND sites post-stroke using two different magnetic resonance imaging (MRI) sequences in a clinically-relevant ovine model.

Methods: 30 Merino sheep (2-3 years) underwent 2h middle cerebral artery occlusion, with MRI (3T Siemens) performed at baseline, and 1-, 3- or 6-months post-stroke (n=10/timepoint; 5F, 5M). BBB permeability was assessed by looking at the difference in gadolinium signal on T1-weighted MRI [MPRAGE, TR/TE: 2000/2.8ms] and Dynamic Contrast Enhance MRI (DCE) [TR/TE: 5.06/1.98]. SND regions of interest were extracted and registered with the FMRIB Software Library (v6.0.7.9; T1W) and Quantiphyse (v0.9.9; DCE).

Results: Processing and analysis protocols have been established for DCE MRI for the first time in sheep, however DCE appears to be highly sensitive and associated with high variability across animals within time-points. T1 pre- and post-gadolinium analysis is currently underway but is predicted to be more reliable given the scan acquisition time and a simpler post-processing procedure. 

Conclusion: We anticipate these findings will both help characterise the profile of BBB permeability changes in post-stroke SND and inform the best MRI sequence to reliably detect and quantify BBB permeability alterations.