부산대학교 도서관

Background, hypothesis: Gyrencephalic large-animal models of acute ischemic stroke (AIS) such as swine gain attention in translating preclinical to clinical stroke research, with brain anatomy similar to humans. Most swine models employ young animals with AIS by permanent occlusion (P-AIS). This does not reflect the, often elderly, stroke patient. Therefore, recanalized AIS (R-AIS) in adult mini-pigs could improve preclinical to clinical translation.Methods: Anesthetized adult (2 yrs) Aachen mini-pigs (n=6) underwent craniotomy to occlude right-side middle cerebral arteries (MCA) with aneurysm clips. Clips were released at 4 hrs to allow recanalization for 2-4 hrs (R-AIS, n=4) or left in place until sacrifice (P-AIS, n=1). 3D angiography confirmed occlusion and recanalization. Infarct size was determined by TTC staining and expressed as % infarct per hemisphere (median, min-max). Qualitative neurovascular histology was performed in HE-stained sections of ischemic and remote (contralateral) tissue.Results: All animals survived until end-of-procedure. In 4 of 5 animals R-AIS successfully induced cortical infarcts (infarct size, 16.2% [9.1%-25.2%]). R-AIS was unsuccessful in 1 animal, with a small striatum infarct (2.7%) without cortical involvement and unclear angiographic occlusion. P-AIS (n=1) resulted in 12.7% infarct. Assessment of ischemic (TTC-neg) tissue revealed characteristic histology of ischemia/reperfusion-derived neurovascular damage, including erythrocyte extravasation, vasostasis, increased perivascular space and intravascular platelet/fibrin aggregates (Figure 1) in all animals. Remote tissue did not show any of these features.Conclusions: Adult Aachen mini-pigs can be used for acute ischemic stroke modelling and display characteristic neurovascular features associated with ischemia and reperfusion. They may serve as a model for translational therapeutic neuro(vascular)-protective research.