Effects of tetrahydrobiopterin on cerebral infarction after transient focal ischemia in rats.
OBJECTIVE
The present study investigated the effects of tetrahydrobiopterin (BH4) on cerebral infarction after transient focal ischemia in rats.


METHODS
Focal ischemia (1·5 hours) was created in male Sprague-Dawley rats (250-280 g)  by middle cerebral artery occlusion. Some rats were treated with 20 mg/kg tetrahydrobiopterin by intraperitoneal injection 30 minutes before reperfusion. At 2, 6, and 12 hours of reperfusion, the brains were harvested for the nitric oxide synthase (NOS) activity and nitric oxide (NO) level  assays. At 12 hours of reperfusion, the brains were harvested for infarct size measurement.


RESULTS
NOS activity and NO level were all augmented after reperfusion. BH4 treatment significantly further increased NOS activity and NO level. Cerebral infarct size was significantly bigger  in BH4 treatment group compared to that in no treatment group.


CONCLUSIONS
The data indicate that BH4 enhances cerebral infarction after transient focal ischemia in rats, through NOS and NO pathway.
Tang
Ling-Ling
LL
First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. lltang72@126.com
Zheng
Jie-Sheng
JS
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000633:toxicity; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D001708:Biopterins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C003402:sapropterin