Influence of Brain Edema on the Antiischemic Effect of D-CPPene in Rat Focal Cerebral Infarction

ABSTRACT

OBJECTIVE: The model of focal ischemia that involves occlusion of middle cerebral artery(MCA) is one of the most commonly used methods in the rat, which can be considered to be equivalent to a focal cerebral infarction in man. Infarction size is often used as the standard to assess potential therapeutic regimens in models of focal cerebral infarction. In practice, scientists have estimated infarction volume by a variety of methods. One of the fundamental problems in measuring infarction volume is the enlargement of infarcted tissue by edema. To minimize the error of overestimation that may be caused by edema, several methods have been proposed. METHOD:The author assessed the antiischemic effect of a competitive N-methyl-D-aspartate(NMDA) antagonist, D-(E)-4-(3-phosphonoprop-2-enyl) piperazine-2carboxylic acid(D-CPPene) in MCA occlusion model in the rat. Four different morphometric analysis were used to measure infarction volume a real measurement, the Swanson's method designed to minimize the error of overestimation, a measurement using a diagram, percentage method (infarction volume divided by the volume of ipsilateral hemisphere), which were to elucidate the effects of each method upon measuring the infarction volume regarding the possible influence of edema. The animals were sacrificed 24 hours after MCA occlusion and the amount of ischemic brain damage was assessed by 8 predetermined coronal planes. RESULT: Post-occlusion treatment of D-CPPene which was initiated 15 minutes after MCA occlusion, produced reduction of infarction volume to about 40% compared to the control(p<0.05). The volume of infarction determined by a real measurement was much larger than that by the Swanson's or diagram method(p<0.05), about 70% larger in the control and 2 times larger in the treated group. However, there was no significant difference in the measured volume between the Swanson's and diagram methods. The protection rate which was obtained by subtracting the infarction volume of the treated from that of the control, was larger by the Swanson's and diagram method than by a real measurement and percentage method. CONCLUSION: These results demonstrate that a competitive NMDA antagonist, D-CPPene which was administered 15 minutes after post-occlusion, has a significant neuroprotective effect on ischemic brain damage in focal cerebral infarction. But it appears to have no specific protective effect on ischemic brain edema. The overestimation of infarction volume at the peak time of brain edema could be substantially reduced by not only the Swanson's method but also the diagram method.