Reductions in mRNA of the neuroprotective agent, neuroserpin, after cerebral ischemia/reperfusion in diabetic rats.
The aim of this study is to investigate disturbances in fibrinolytic components in diabetic rats with middle cerebral artery occlusion (MCAO). Comparison of cerebral injury at 23 h after reperfusion indicated that infarction volumes were increased in diabetic rats as compared with normal rats. Cerebral ischemia/reperfusion in normal and diabetic rats was accompanied by increased expression of tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1) and neuroserpin (NSP) mRNA after reperfusion. Most importantly, the expression of NSP mRNA, but not t-PA, u-PA and PAI-1 mRNA, was reduced to undetectable levels at 11 and 23 h after reperfusion in diabetic rats as compared with normal rats. Although activity of PA (t-PA and u-PA) and the ratio of PA/PAI were increased at 5 h after reperfusion in both ischemic brains of diabetic and normal rats, the levels in diabetic rats were lower than that in normal rats. We speculate that the exacerbation of ischemic injury in diabetic rats may be related to the reduction of fibrinolytic component and the neuroprotective role of NSP. Further study of the efficacy of NSP in the pathogenesis and treatment of cerebral ischemia may provide novel insights.
Liang
Wang
W
Institute of Neurology, Fudan University, 12 Wulumuqi Zhong Road, 200040, Shanghai, China.
Chuan-Zhen
Lu
L
Qiang
Dong
D
Jian
Qiao
Q
Hui-Min
Ren
R
Bao-Guo
Xiao
X
D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D000097522:Neuroserpin
D009479:Neuropeptides; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D000097522:Neuroserpin