Background
Secondary neurodegeneration (SND) develops weeks to months post-stroke in regions distal to the primary infarct, associated with post-stroke cognitive decline. SND has been shown within the ipsilateral thalamus and hippocampus, typically within 3 months post-stroke. However, the spatiotemporal profile of how these mechanisms occur is still poorly understood, and there are no reports in a clinically-relevant large animal stroke model. As such, this study sought to determine the degree of brain atrophy at SND sites post-stroke in an ovine model.
Methods
Thirty merino sheep (2-3 years old; n=5M,5F/gp) underwent 2-hour transient middle cerebral artery occlusion with reperfusion. Using MRI (3T Skyra, Siemens Healthineers), T1-weighted structural scans were acquired pre-stroke and at 1-, 3- or 6-months post-stroke. Volumes of ipsilateral and contralateral thalamus, hippocampus, prefrontal cortex, amygdala, basal ganglia and hemispheres were manuallytraced and quantified using neuroimaging segmenting software ITK-snap.
Results
Hemispheric volumes (ipsilateral and contralateral) were significantly decreased from pre-stroke levels at 1- (p≤0.0185), 3- (p≤0.01) and 6-months (p≤0.0009) post-stroke. This pattern was similar in the thalamus (1M, p<0.0001; 3M,p≤0.0037; and 6M, p<0.0001) and hippocampus (1M,p<0.0001; 3M, p<0.0004; and 6M, p=0.0024; ipsilateral hippocampus only). Volumetric analysis of the basal ganglia, amygdala and pre-frontal cortices is ongoing.
Conclusions
We observed increased bilateral brain atrophy in the hemispheres, thalamus and hippocampus from 1-month post-stroke onwards, demonstrating that SND pathology is not confined to the stroke hemisphere. Such evidence is key in understanding when and where SND occurs post-stroke and to develop targeted treatments to improve long-term outcomes.