Establishment and characterization of porcine focal cerebral ischemic model induced by endothelin-1

Background and purpose: Due to well-developed Circle of Willis in pigs, it is technically challenging to make persistent focal ischemic stroke based on occlusion of cerebral arteries. Endothelin-1 could cause a focal lesion by forcing transient but strong vasoconstriction in the circumscribed injected area. Its use in porcine stroke model has drawn attention lately. However, all the porcine endothelin-1 induced models were euthanized soon after surgery. Whether the brain lesion is persistent, and whether they could cause neurological deficit are not known. This research aims to provide a more detailed characterization of endothelin-1 induced porcine cerebral ischemic model by evaluating the change of neurological function and the brain lesion monitored by MRI of the pigs. Methods: Danish Domestic pigs were randomly divided into two groups: a group receiving endothelin-1 (ET-1 group, n = 6) and a sham group (n = 6). After the fronto-temporal craniotomy, pigs in the ET-1 group received 200 mu l endothelin-1 injected within a cortical area of one cm(2); pigs in the sham group received only saline injections. Neurological deficit evaluation and MRI scanning were done 24 h and 72 h after operation. Afterwards, hematoxylin and eosin staining was conducted to detect the morphological characteristics of the damaged brain tissue. Results: The average performance score in the pigs of the ET-1 group was 9.67 +/- 1.03 and 9.00 +/- 1.26 respectively, at 24 h and 72 h after surgery, which was significantly higher than that of the pigs in sham group. The brain lesion percentage detected by MRI was 12.26 +/- 0.60%, and 10.33 +/- 0.51% respectively, at 2411 and 72 h after surgery in the ET-1 group. Microscopy showed extended pyknotic neuronal perikarya in neurons located in the ischemic area. Conclusions: The endothelin-1 induced porcine cerebral ischemic model is technically easier, and able to create cerebral ischemia severe enough to cause a functional neurological deficit as well as observable lesions on MRI. It is a suitable model for long-term cerebral ischemia research. (C) 2016 Elsevier Ireland Ltd. All rights reserved.