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Summary: Middle cerebral artery occlusion was per formed in rats while the animals were inside the nuclear magnetic resonance (NMR) tomograph, Successful occlu sion was confirmed by the collapse of amplitude on an electrocorticogram, The ultrafast NMR imaging tech nique UFLARE was used to measure the apparent diffu sion coefficient (ADC) immediately after the induction of cerebral ischemia, ADC values of normal cortex and cau date-putamen were 726 ± 22 x 10-6 mm2/s and 659 ± 17 x 10-6 mm 2 /s, respectively, Within minutes of occlu sion, a large territory with reduced ADC became visible in the ipsilateral hemisphere, Over the 2 h observation period, this area grew continuously, Quantitative analysis of the ADC reduction in this region showed a gradual ADC decrease from the periphery to the core, the lowest ADC value amounting to about 60% of controL Two hours after the onset of occlusion, the regional distribu tion of ATP and tissue pH were determined with biolu minescence and fluorescence techniques, respectively. There was a depletion of A TP in the core of the ischemic Diffusion-weighted nuclear magnetic resonance (NMR) imaging (DWI) has been shown to be sensi tive to cerebral ischemia during the early, acute

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The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 microns resolution. Each 75 x 75 microns digitized image pixel was then converted into the appropriate units of either protein synthesis, ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 +/- 12.0 ml 100 g-1 min-1 and that of energy failure was 18.5 +/- 9.8 ml 100 g-1 min-1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 +/- 9.6 and 56.0 +/- 6.5 ml 100 g-1 min-1, respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 +/- 9.7 ml 100 g-1 min-1 (p less than 0.05 compared to 1 h ATP threshold value; all values are mean +/- SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary: Following permanent occlusion of the left middle cerebral artery (MCA) in rats, electrophysiologi cal and hemodynamic characteristics of the periinfarct border zone were investigated in sham-operated (n = 6), untreated (n = 6), and MK-801-treated 0.0 mg/kg; n = 6) animals. For this purpose, direct current potential (DC), EEG, and blood flow (laser-Doppler flowmetry) were re corded from the cortex in the periphery of the MCA ter ritory. In sham-operated rats, a single negative cortical DC deflection was observed after electrocoagulation of the cortex, whereas in untreated MCA-occluded animals, three to eight transient DC det1ections were monitored during the initial 3 h of ischemia. The duration of these cortical DC shifts gradually increased from 1.2 ± 0.3 to 3.7 ± 2.7 min (mean ± SD; p < 0.05) during this time. In animals treated intraperitoneally with MK-801 (3.0 mgt According to the classic concept of the threshold relationship between the density of ischemia and neuronal injury, different flow thresholds have been identified for the suppression of membrane poten tials and the suppression of neuronal transmission (Astrup et aI., 1977). Tissue perfused at a flow rate between these thresholds is referred to as the isch emic penumbra because the neurons in this area are thought to be functionally inactive but still viable (Astrup et aI., 1981 ). Threshold determinations of brain metabolism have revealed that the flow rate

The evolution of brain infarction after transient focal cerebral ischemia was studied in mice using multiparametric imaging techniques. One-hour focal cerebral ischemia was induced by occluding the middle cerebral artery using the intraluminal filament technique. Cerebral protein synthesis (CPS) and the regional tissue content of adenosine triphosphate (ATP) were measured after recirculation times from 0 hours to 3 days. The observed changes were correlated with the expression of the mRNAs of hsp-70, c-fos, and junB, as well as the distribution of DNA double-strand breaks, visualized by TUNEL. At the end of 1 hour of ischemia, protein synthesis was suppressed in a larger tissue volume than ATP in accordance with the biochemical differentiation between core and penumbra. Hsp70 mRNA was selectively expressed in the cortical penumbra, whereas c-fos and junB mRNAs were increased both in the lateral part of the penumbra and in the ipsilateral cingulate cortex with normal metabolism. During reperfusion after withdrawal of the intraluminal filament, suppression of CPS persisted except in the most peripheral parts of the middle cerebral artery territory, in which it recovered between 6 hours and 3 days. ATP, in contrast, returned to normal levels within 1 hour but secondarily deteriorated from 3 hours on until, between 1 and 3 days, the ATP-depleted area merged with that of suppressed protein synthesis leading to delayed brain infarction. Hsp70 mRNA, but not c-fos and junB, was strongly expressed during reperfusion, peaking at 3 hours after reperfusion. TUNEL-positive cells were detected from 3 hours on, mainly in areas with secondary ATP depletion. These results stress the importance of an early recovery of CPS for the prevention of ischemic injury and suggest that TUNEL is an unspecific response of delayed brain infarction.

The effect of various anesthetics on the functional-metabolic coupling of cerebral cortex was studied in rats submitted to unilateral somatosensory stimulation. The regional cerebral metabolic rate of glucose (CMRglc) was measured autoradiographically using the 2-deoxyglucose method, and somatosensory activation was carried out by electrical stimulation of the left forepaw. In animals treated with 70% nitrous oxide, 0.5% halothane/70% nitrous oxide or 40 mg/kg pentobarbital, CMRglc of somatosensory cortex did not change despite generation of primary evoked cortical potentials. Anesthesia with 80 mg/kg alpha-chloralose, in contrast, led to a focal increase of CMRglc in the primary somatosensory cortex from 52.1 +/- 18.3 to 73.1 +/- 18.9 mumol/100 g/min (means +/- s.d.). Metabolic activation was strictly confined to the forelimb (FL) area of somatosensory cortex, and it exhibited a laminar pattern with maximal activation in layers I, II and IV. The preservation of functional-metabolic coupling under a surgical dose of chloralose renders this anesthetic particularly suited for the investigation of coupling processes under conditions where the experimental requirements preclude the use of unanaesthetized animals.

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