A REPRODUCIBLE MODEL OF MIDDLE CEREBRAL-ARTERY OCCLUSION IN MICE - HEMODYNAMIC, BIOCHEMICAL, AND MAGNETIC-RESONANCE-IMAGING

A reproducible model of thread occlusion of the middle cerebral artery (MCA) was established in C57 Black/6J mice by matching the diameter o f the thread to the weight of the animals. For this purpose, threads o f different diameter (80 to 260 mu m) were inserted into the MCA of an imals of different weights (18 to 33 g), and the success of vascular o cclusion was evaluated by imaging the ischemic territory on serial bra in sections with carbon black. Successful occlusion of the MCA resulte d in a linear relationship between body weight and thread diameter (r = 0.46, P < 0.01), allowing precise selection of the appropriate threa d size. Laser-Doppler measurements of CBF, neurological scoring, and 2 ,3,5-triphenyltetrazolium chloride staining confirmed that matching of animal weight and suture diameter produced consistent cerebral infarc tion. Three hours after MCA occlusion, imaging of ATP, tissue pH, and cerebral protein synthesis allowed differentiation between the central infarct core, in which ATP was depleted, and a peripheral penumbra wi th reduced protein synthesis and tissue acidosis but preserved ATP con tent. Perfusion deficits and ischemic tissue alterations could also be detected by perfusion-and diffusion-weighted magnetic resonance imagi ng, demonstrating the feasibility of dynamic evaluations of infarct ev olution. The use of multiparametric imaging techniques in this improve d MCA occlusion model opens the way for advanced pathophysiological st udies of stroke in gene-manipulated animals.