NEUROPROTECTIVE EFFECT OF THE NOVEL GLUTAMATE AMPA RECEPTOR ANTAGONIST YM872 ASSESSED WITH IN-VIVO MR-IMAGING OF RAT MCA OCCLUSION

The neuroprotective effect of post-ischemic treatment with the novel, highly water-soluble, glutamate AMPA receptor antagonist YM872 was eva luated by using MR imaging and histopathology of rats subjected to per manent MCA occlusion. Two treatment groups with continuous i.v. infusi on of 20 mg kg(-1) h(-1) YM872 during either the first 4 h or first 24 h after MCA occlusion, called 4 h YM872 treatment group (n = 9) and 2 4 h YM872 treatment group (n = 8) respectively, were compared to a con trol group (n = 8). The main end-point was T2 weighted MR imaging and histopathology 24 h after MCA occlusion. Also the time evolution of th e ischemic tissue damage was studied by diffusion weighted MR imaging 41/2 and 24 h after MCA occlusion. The volume of ischemic tissue damag e as assessed by diffusion weighted MR imaging 41/2 h after MCA occlus ion was significantly smaller in both YM872 treatment groups (99 +/- 5 2 mm(3) and 102 +/- 44 mm(3) compared to 186 +/- 72 mm(3) in the contr ol group, +/- S.D. and p = 0.008). The infarct volume as assessed by T 2 weighted MR imaging 24 h after MCA occlusion was significantly small er only in the 24 h YM872 treatment group (262 +/- 57 mm(3) compared t o 366 +/- 49 mm(3) in the control group, +/- S.D. and p = 0.01) while the infarct volume in the 4 h YM872 treatment group (357 +/- 88 mm(3)) was similar to the control group. YM872 treatment significantly reduc ed the infarct volume 24 h after MCA occlusion when the drug was admin istered as continuous infusion during the 24-h observation period. (C) 1998 Elsevier Science B.V. All rights reserved.