Mice deficient in cytosolic phospholipase A2 are less susceptible to cerebral ischemia/reperfusion injury.
To determine the role of cytosolic phospholipase A2 (cPLA2) in infarct development, wild-type and cPLA2 knock-out mice were subjected to focal cerebral ischemia for 75 min by occluding the middle cerebral artery using nylon filament and subsequent reperfusion by withdrawing the filament. The neurological deficit severity was evaluated by a modified 4-point scale. After the reperfusion period (72 h), mice were killed, and the brains were cut into four 2 mm coronal sections using a rodent brain matrix. Sections were stained with 2% 2,3,5-triphenyltetrazolium chloride (TTC). The infarct volume was 87.19 +/- 27.54 mm3 (mean +/- SD, n = 11) in the wild-type mice and 48.20 +/- 31.32 mm3 (n = 10; P < 0.01 vs. wild-type) in the knock-out mice. Less severe functional neurological deficits were observed in knock-out mice at 72 h after ischemia when compared with wild-type. Thus, disruption of cPLA2 resulted in significant reduction of infarct area and neurological deficit severity in the MCA occlusion model. These data indicate a critical role for cPLA2 in the pathogenesis of cerebral ischemia/ reperfusion injury.
Tabuchi
S
S
Department of Neurosurgery, Institute of Neurological Sciences, Tottori University School of Medicine, Yonago, Japan. stabuchi@gj8.so-net.ne.jp
Uozumi
N
N
Ishii
S
S
Shimizu
Y
Y
Watanabe
T
T
Shimizu
T
T
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000209:etiology* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D002560:Cerebrovascular Circulation; D003600:Cytosol / Q000201:enzymology*; D004198:Disease Susceptibility; D051379:Mice; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D010741:Phospholipases A / Q000172:deficiency*; D054467:Phospholipases A2; D015427:Reperfusion Injury / Q000150:complications / Q000209:etiology* / Q000503:physiopathology
D010741:Phospholipases A; D054467:Phospholipases A2