The evolution of
brain infarcts during permanent occlusion of the middle cerebral artery (MCA) was studied in mice using multiparametric imaging techniques. Regional
protein synthesis and the regional tissue content of
ATP were measured on adjacent cryostat sections at increasing intervals after vascular occlusion ranging from 1 hour to 3 days. The observed changes were correlated with the expression of the
mRNA of hsp70, c-fos, c-jun, and junB, as well as the distribution of
DNA double-strand breaks visualized by
terminal deoxynucleotidyl transferase-mediated dUTP-
biotin nick end labelling (TUNEL). One hour after MCA occlusion, the tissue volume with suppressed
protein synthesis was distinctly larger than that in which
ATP was depleted. With ongoing
ischemia time, the
ATP-depleted area gradually expanded and, within 1 day, merged with the region of suppressed
protein synthesis. Expression of hsp70
mRNA occurred mainly in the penumbra (defined as the region of suppressed
protein synthesis but preserved
ATP), peaking at 3 hours after vascular occlusion. Expression of the immediate-early genes c-jun, c-fos, and junB increased both in the penumbra and the periinfarct normal tissue already at 1 hour after vascular occlusion, with slightly different regional and temporal patterns for each of these genes.
DNA fragmentations were clearly confined to neurons; they appeared after 1 day in the
infarct core (defined as the region of suppressed
ATP) and never were detected in the penumbra. The late appearance of TUNEL after
infarcts had reached their final size and the absence in the penumbra points against a major pathogenetic role of apoptosis. Permanent MCA occlusion in mice thus produces a gradually expanding
infarct, the final size of which is heralded by the early inhibition of
protein synthesis.