The Efficacy of Retrograde Infusion with LY231617 in a Rat Middle Cerebral Artery Occlusion Model

     Nobuhiro Inoue, Y Lucas Yamamoto, Yasushi Ito, James A Clemens, Jill K Panetta and Mirko Diksic

Abstract:   Background and Purpose: 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=6) received saline (86 ml/min) by retrograde infusion of the cerebral vein (RICV). Group D (n=22) was administered LY231617 (10mg/kg/2hr) in saline (86ml/min) by RICV. Local cerebral blood flow with [¹⁴C]-iodoantipyrine and blood-brain transfer constant with ¹⁴C-a-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. Conclusion: Retrograde infusion of the cerebral vein with LY231617 resulted in a significant amelioration at seven hours post MCA occlusion.

Can. J. Neurol. Sci. 1996; 23: 175-183