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The relationship between local cerebral glucose utilization (LCMR glc ) and local CBF (LCBF) is known to be disturbed in regions surrounding an acute focal ischemic lesion—areas that undergo repeated transient depolarizations. In this study, we evaluated the relationship between LCMR glc  and LCBF in the acute focal ischemic penumbra to quantify metabolism–flow uncoupling, and we related these findings to local electrophysiological measurements. A novel strategy utilizing three-dimensional (3D) autoradiographic image averaging yielded group 3D reconstructions of LCBF, LCMR glc , and the CMR/CBF ratio. The distal right middle cerebral artery of Sprague-Dawley rats was occluded by laser-driven photothrombosis following administration of the photosensitizing dye rose bengal; this was coupled with permanent ipsilateral and 1-h contralateral common carotid artery occlusions. LCBF (n = 7) and LCMR glc  (n = 7) were measured autoradiographically at 1.25 and 1.5–2 h postocclusion, respectively, in matched animal groups. Within the ischemic penumbra (defined as having LCBF of 20–40% of control or 0.23–0.47 ml g −1  min −1 ), LCMR glc  showed a heterogeneous pattern with values ranging from near normal to markedly increased. The resulting CMR glc /CBF ratio in this zone was 234 ± 100 μmol/100 ml (mean ± SD), representing a severe degree of metabolism-flow dissociation when compared with the CMR glc /CBF ratio of 51.0 ± 28.7 μmol/100 ml of the contralateral (normal) hemisphere. Metabolism–flow uncoupling was confined to the ipsilateral cortex and was most prominent at the anterior and posterior coronal poles of the ischemic lesion. In the frontoparietal penumbra, where marked uncoupling was observed, sustained deflections of the DC potential were recorded, which increased significantly in duration over the initial 65 min postocclusion. Both the heterogeneous pattern of LCMR glc  and the widespread distribution of increased CMR glc /CBF ratio in the ischemic penumbra are thought to reflect the metabolic consequences of periinfarct depolarizations. Analysis of averaged 3D autoradiographic data sets provides a powerful means for assessing metabolism-flow uncoupling surrounding an ischemic focus.

journal of cerebral blood flow and metabolism

Three-Dimensional Image Analysis of Brain Glucose Metabolism-Blood Flow Uncoupling and its Electrophysiological Correlates in the Acute Ischemic Penumbra following Middle Cerebral Artery Occlusion