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 200μl endothelin-1 injected within a cortical area of one cm2; pigs in the sham group received only saline injections. Neurological deficit evaluation and MRI scanning were done 24h and 72h 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 24h and 72h 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 24h and 72h 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.