Titration of postischemic cerebral hypoperfusion by variation of ischemic severity in a murine model of stroke.

Abstract

Murine models using intraluminal occluding sutures to establish transient focal cerebral ischemia are becoming increasingly widespread, because of advances in transgenic technology and the advent of cerebroprotective strategies to ameliorate postischemic cerebrovascular no-reflow. We hypothesize that the degree of postischemic hypoperfusion is directly related to the severity of the initial ischemic insult. Transient ischemia of 45-minute duration was produced using middle cerebral artery occlusion with 10-0 (n = 5), 9-0 (n = 5), 8-0 (n = 6), 7-0 (n = 8), 6-0 (n = 30), or 5-0 (n = 5) sutures. In separate experiments, transient vessel occlusion with 6-0 sutures was performed for 15 (n = 17), 30 (n = 16), or 45 (n = 30) minutes. Sequential laser Doppler measurements of relative cerebral blood flow were obtained, and stroke severity was assessed using neurological deficit scores and infarction volumes. Although relative cerebral blood flow at the time of occlusion and 24 hours thereafter was diminished in parallel with increasing suture diameters, only the use of larger sutures resulted in postischemic no-reflow. As the suture diameter was increased, the resultant reflow was decreased and the stroke outcome worsened. A more than twofold increase in infarction volume (8.0 +/- 3 versus 19.7 +/- 3%, P < 0.05) resulted when ischemia duration was increased from 30 to 45 minutes. Titration of the initial ischemic insult leads to corresponding variations in the magnitude of postischemic no-reflow and tissue damage. Therefore, critical control of the severity of the initial injury in studies using intraluminal suture occlusion is warranted.