The efficacy of retrograde infusion with LY231617 in a rat middle cerebral artery occlusion model.
OBJECTIVE
We examined the efficacy of the antioxidant LY231617 administered five hours following middle cerebral artery (MCA) occlusion in rats.


METHODS
The treatment was contrived for a two hour interval. Group A (n = 16) was left untreated. Group B (n = 16) received an intravenous infusion of LY231617. Group C (n = 16) received saline (86 microliters/min) by retrograde infusion of the cerebral vein (RICV). Group D (n = 22) was administered LY231617 (10mg/kg/2 hr) in saline (86 microliters/min) by RICV. Local cerebral blood flow with [14C]-iodoantipyrine and blood-brain transfer constant with 14C-alpha-amino-isobutyric acid were examined. Early ischemic damage was histologically examined with cresyl violet and Luxol fast blue and with triphenyl-tetrazolium chloride.


RESULTS
The results revealed a marked increase in local cerebral blood flow (over 600%, p < 0.01) after RICV with LY231617, with a significant improvement of BBB permeability in rats from group D. Ischemic brain damage measured with Luxol fast blue and triphenyl-tetrazolium chloride methods showed a significant improvement (50-91%) of ischemic damage in group D, as compared to groups B and C.


CONCLUSIONS
Retrograde infusion of the cerebral vein with LY231617 resulted in a significant amelioration at seven hours post MCA occlusion.
Inoue
N
N
Neuroisotope Laboratory, Mc Gill University, Montreal, Quebec, Canada.
Yamamoto
Y L
YL
Ito
Y
Y
Clemens
J A
JA
Panetta
J K
JK
Diksic
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001345:Autoradiography; D002545:Brain Ischemia / Q000188:drug therapy*; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D002084:Butylated Hydroxytoluene; C081064:LY 231617