L-arginine in focal cerebral ischemia

Abstract

Nitric oxide and its precursor, L-arginine, have a great importance in cerebrovascular studies. In this study, we elucidate the dose dependent L-arginine effects on cerebral ischemia. The study involved 96 New Zealand albino rabbits, which were randomly allocated into four groups. The middle cerebral artery was occluded after a modified transorbital approach. Before the occlusion of MCA, each group was intravenously administered three doses of L-arginine i.e. 2.5 mg kg-1 for Group 1, 7.5 mg kg-1 for Group 2, and 12.5 mg kg-1 for Group 3. Thus, each group consisting of 24 animals was listed as 2.5 mg kg-1 (Group 1), 7.5 mg kg-1 (Group 2), 12.5 mg kg-1 (Group 3), and control group (receiving no intervention). Cerebral tissue oxygenization was measured in parietal area by near infrared spectroscopy in all animals prior to and at 5, 30, and 60 min after MCA occlusion. Six hours after MCA occlusion, all the animals were studied for the area of ischemia (n = 40), edema formation (n = 32), and blood nitrite-nitrate levels (n = 24). At the dose of 2.5 mg kg-1 of L-arginine no differences were detected on ischemic tissue volume, brain edema, cerebral tissue oxygenization, blood nitrite-nitrate levels when compared to the values of control group. However, with the dose of 7.5 mg kg-1, there were significant improvements in the levels of ischemic tissue volume, brain edema, and nitrite-nitrate levels compared to those of the control group and the 2.5 mg kg-1 group. At a dose of 12.5 mg kg-1, there were further improvements in the levels of ischemic tissue volume, brain edema, penumbral zone nitrite-nitrate levels. After 30 min of occlusion, cerebral tissue oxygenization values increased in a dose dependent fashion. L-arginine's protective effect on cerebrovascular ischemia shows a dose dependent effect on infract size and tissue water content that may prove beneficial in the treatment of ischemia. However, further dose-dependent studies are needed.