Abstract
Modeling stroke in animals is essential for testing efficacy of new treatments; however, previous neuroprotective therapies, based on systemic delivery in rodents failed, exposing the need for model with improved clinical relevance. The purpose of this study was to develop endovascular approach for inducing ischemia in swine. To achieve that goal, we used intra-arterial administration of thrombin mixed with gadolinium and visualized the occlusion with real-time MRI. Placement of the microcatheter proximally to rete allowed trans-catheter perfusion of the ipsilateral hemisphere as visualized by contrast-enhanced perfusion MR scans. Dynamic T2*w MRI facilitated visualization of thrombin + Gd solution transiting through cerebral vasculature and persistent hyperintensities indicated occlusion. Area of trans-catheter perfusion dynamically quantified on representative slice before and after thrombin administration (22.20 ± 6.31 cm2 vs. 13.28 ± 4.71 cm2 respectively) indicated significantly reduced perfusion. ADC mapping showed evidence of ischemia as early as 27 min and follow-up T2w scans confirmed ischemic lesion (3.14 ± 1.41 cm2). Animals developed contralateral neurological deficits but were ambulatory. Our study has overcome long lasting challenge of inducing endovascular stroke model in pig. We were able to induce stroke using minimally invasive endovascular approach and observe in real-time formation of the thrombus, blockage of cerebral perfusion and eventually stroke lesion.
Highlights
Ischemic stroke is a third leading cause of death and the leading cause of long-term serious disability in a dults[1]
Due to similarities in cerebral vasculature dogs are excellent for modeling stroke using endovascular a pproach[14], but being companion animals are socially controversial as research subjects, and, in many countries experimentation using dogs is not allowed any more
Due to these positive features pig has been used for modeling of stroke; the only reliable stroke model in swine so far was based on surgical access to the middle cerebral artery (MCA)
Summary
Ischemic stroke is a third leading cause of death and the leading cause of long-term serious disability in a dults[1]. Mechanical thrombectomy substantially extended the therapeutic window up to 24 h in selected patients, which increased the number of eligible patients[3] Despite these positive developments burden of stroke remains high. Domestic pig is considered excellent for modeling neurological disease because it has relatively large gyrencephalic brain, only seven times smaller than human brain and white–gray matter ratio and immune system closely resembles that in h uman[15]. Due to these positive features pig has been used for modeling of stroke; the only reliable stroke model in swine so far was based on surgical access to the middle cerebral artery (MCA).
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