A new model of focal cerebral ischemia in the miniature pig.
OBJECTIVE
The purpose of this set of studies is to design a minimally invasive, reproducible stroke model in the gyrencephalic brain. This paper provides information on both surgical technique and methods of quantification of ischemic damage to both gray and white matter in the miniature pig.


METHODS
Sixteen male miniature pigs were randomly divided into three groups and underwent transcranial surgery involving a frontotemporal approach with orbital rim osteotomy for permanent middle cerebral artery occlusion (MCAO; five animals), permanent internal carotid artery occlusion (ICAO; six animals), and a sham operation (five animals). Histological mapping and magnetic resonance (MR) imaging were used to delineate the areas of ischemic damage. The volumes of infarction measured directly from MR images were 16.2 +/- 1.1, 1.5 +/- 0.5, and 0.0 +/- 0.0 cm3 (mean +/- standard deviation [SD], p < 0.001) in the MCAO, ICAO, and sham-operated groups, respectively. The areas of ischemia identified through histological analysis and MR imaging showed a good correlation (r2 = 0.86, p < 0.0001). Immunohistochemical staining with an amyloid precursor protein (APP) antibody was used to evaluate axonal damage and calculate a total APP score for axonal damage of 44.8 +/- 2.9 in the MCAO, 13.2 +/- 6.6 in the ICAO, and 0.0 +/- 0.0 (mean +/- SD, p < 0.002) in the sham-operated animals.


CONCLUSIONS
This new model of focal cerebral ischemia induces a reproducible amount of ischemic damage in both gray and white matter, and has significant utility for studies of the pathophysiology of ischemia in the gyrencephalic brain and for assessment of the therapeutic efficacy of drugs prior to the initiation of human clinical trials.
Imai
Hideaki
H
Department of Neurosurgery, Institute of Experimental Animal Research, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. hideimai@showa.gunma-u.ac.jp
Konno
Kenjiro
K
Nakamura
Mitsunobu
M
Shimizu
Tatsuya
T
Kubota
Chisato
C
Seki
Koji
K
Honda
Fumiaki
F
Tomizawa
Shinichiro
S
Tanaka
Yukitaka
Y
Hata
Hidekazu
H
Saito
Nobuhito
N
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology* / Q000662:veterinary; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D020768:Middle Cerebral Artery / Q000473:pathology / Q000601:surgery; D010027:Osteotomy; D011897:Random Allocation; D015203:Reproducibility of Results; D013552:Swine; D013556:Swine, Miniature