Inducible nitric oxide synthase expression in the ischemic core and penumbra after transient focal cerebral ischemia in mice.
The present observations examined the hypothesis that the iNOS expression in the ischemic penumbra after a transient focal ischemic insult is involved in the recruitment of penumbra into infarction. The middle cerebral artery in mice was occluded for 2 h by an intraluminal filament and then recirculated. The measurement of iNOS activity, iNOS protein formation and NO concentration in the ischemic core and penumbra, and the determination of infarct volume were performed at 6, 12, 24 and 48 h after reperfusion. iNOS protein and iNOS enzymatic activity appeared at 6 h, peaked at 24 h, and declined at 48 h in the penumbra after reperfusion. iNOS protein was not detectable in contralateral area and in sham-operated brains. The time course of iNOS protein, enzymatic activity and NO concentration in the penumbra but not in the core matched the process of infarct maturation. Treatment with iNOS inhibitor aminoguanidine (100 mg.kg(-1), i.p.) at 6 and 12 h after reperfusion inhibited iNOS activity by 88.0 +/- 10.4% and reduced NO concentration by 48.5 +/- 8.3% in the penumbra, and lessened infarct size by 48.8 +/- 7.2%. The iNOS activity and NO level in the core were not affected by the administration of aminoguanidine. These results suggest that iNOS expression in the ischemic penumbra is involved in the recruitment of penumbra into infarction and thereby contributing to the enlargement of infarct.
Zhu
Dong-Ya
DY
Pharmacology Department, New Drug Research Center, China Pharmaceutical University, Tong Jia Xiang 24#, Nanjing 210009, China. dyzhu2002@yahoo.ca
Deng
Qiang
Q
Yao
Hong-Hong
HH
Wang
Dong-Chun
DC
Deng
Ying
Y
Liu
Guo-Qing
GQ
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology; D002544:Cerebral Infarction / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D011897:Random Allocation; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology; D013997:Time Factors
D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C004479:pimagedine