Summary: In focal ischemia of rats, the volume of ischemic lesion correlates with the number of peri-infarct depolariza tions, To test the hypothesis that depolarizations accelerate in farct growth, we combined focal ischemia with externally evoked spreading depression (SD) waves, Ischemic brain in farcts were produced in halothane-anaesthetized rats by intra luminal thread occlusion of the middle cerebral artery (MCA), In one group of animals, repeated SDs were evoked at IS-min intervals by microinjections of potassium acetate into the fron tal cortex, In another group, the spread of the potassium-evoked depolarizations was prevented by application of the N-methyl D-aspartate (NMDA) receptor antagonist dizocilpine (MK-80 I), The volume of ischemic lesion was monitored for 2 h by diffusion-weighted imaging (DWI) and correlated with electro physiological recordings and biochemical imaging techniques, In untreated rats, each microinjection produced an SD wave and a stepwise rise of the volume and signal intensity of the In focal cerebral ischemia of rat infarct size correlates with the number of peri-infarct spreading depression (SD)-like depolarizations (Mies et aI., 1993; Chen et aI., 1993). These depolarizations are generated in the border zone of the ischemic lesion and spread into the peri infarct surrounding (Nedergaard and Hansen, 1993; Ne dergaard and Astrup, 1986). Glutamate antagonists such as dizocilpine (MK-801) or 2,3-dihydroxy-6-nitro-7-Received January I L 1996; final received May 3. 1996; accepted May 29, 1996.Address correspondence. and reprint requests to Prof. Dr. K.-A. Hossmann, Max-Planck-Institut fUr neurologische Forschung. Gleuelerstrasse 50, D-50931 Kiiln, FR Germany.Abbreviations used: ADC, apparent diffusion coefficient; ANOY A. analysis of variance; DC, direct current; DWl, diffusion-weighted im aging; MCA, middle carotid artery; MR, magnetic resonance; NBQX, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F)-quinoxaline; NMDA, N methyl-D-aspartate; RF, radiofrequency; ROI, region of interest; SD, spreading depression; TE. spin echo. 1090DWI-visible cortical lesion, The volume of this lesion in creased between IS min and 2 h of MCA occlusion from 19 ± 15% to 66 ± 16% of ipsilateral cortex, In dizocilpine-treated animals, microinjections of potassium did not evoke SDs, nor did the volume and signal intensity of the DWI-visible cortical lesion change, At 15 min after MCA occlusion, the DWI visible lesion was larger than in untreated animals-43 ± 16% of the ipsilateral cortex; however, after 2 h, it increased only slightly further to 49 ± 21 %. Slower lesion growth in the ab sence of SDs was also reflected by the volume of ATP-depleted tissue, which, after 2 h of MCA occlusion, involved 26 ± 12% of the ipsilateral cortex in treated and 49 ± 9% in untreated animals (p < 0.(1). These observations support the hypothesis that peri-infarct depolarizations accelerate cerebral infarct growth.

The effect of thrombolytic therapy was studied in rats submitted to thromboembolic stroke by intracarotid injection of autologous blood clots. Thrombolysis was initiated after 15 minutes with an intracarotid infusion of recombinant tissue-type activator (10 mg/kg body weight). Reperfusion was monitored for 3 hours using serial perfusion- and diffusion magnetic resonance imaging, and the outcome of treatment was quantified by pictorial measurements of ATP, tissue pH, and blood flow. In untreated animals, clot embolism resulted in an immediate decrease in blood flow and a sharp decrease in the apparent diffusion coefficient (ADC) that persisted throughout the observation period. Thrombolysis successfully recanalized the embolized middle cerebral artery origin and led to gradual improvement of blood flow and a slowly progressing reversal of ADC changes in the periphery of the ischemic territory, but only to transient and partial improvement in the center. Three hours after initiation of thrombolysis, the tissue volume with ADC values less than 80% of control was 39 +/- 22% as compared to 61 +/- 20% of ipsilateral hemisphere in untreated animals (means +/- SD, P = .03) and the volume of ATP-depleted brain tissue was 25 +/- 31% as compared to 46 +/- 29% in untreated animals. Recovery of ischemic brain injury after thromboembolism is incomplete even when therapy is started as early as 15 minutes after clot embolism. Possible explanations for our findings include downstream displacement of clot material, microembolism of the vascular periphery, and events associated with reperfusion injury.

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Diffusion‐weighted proton MR spectroscopy and imaging have been applied to a rat brain model of unilateral middle cerebral artery occlusion between 1 and 4 hr post occlusion. Similar apparent diffusion coefficients (ADC) of most metabolites were observed within each hemisphere. In the ischemic ipsilateral hemisphere, the ADCs were (0.083–0.116) · 10–3 mm2/sec for lactate (Lac), alanine (Ala), γ‐amino butyric acid (GABA), N‐acetyl aspartate (NAA), glutamine (Gln), glutamate (Glu), total creatine (tCr), choline‐containing compounds (Cho), and myo‐inositol (Ins), in the contralateral hemisphere (0.138–0.158) · 10–3 mm2/sec for NAA, Glu, tCr, Cho, and Ins. Higher ADCs was determined for taurine (Tau) in the ipsilateral (0.144 · 10–3 mm2/sec) and contralateral (0.198 · 10–3 mm2/sec) hemisphere. In the ischemic hemisphere, a relative ADC decrease to 65–75% was observed for NAA, Glu, tCr, Cho, Ins and Tau, which was similar to the decrease of the water ADC (to 67%). The results suggest a common cause of the observed ADC changes and provide a broader experimental basis to evaluate theories of water and metabolite diffusion. Magn Reson Med 45:383–389, 2001. © 2001 Wiley‐Liss, Inc.

Somatosensory evoked potentials (SEP) and T* 2-weighted nuclear magnetic resonance (NMR) images were recorded simultaneously during somatosensory stimulation of rat to investigate the relationship between electrical activation of the brain tissue and the signal intensity change in functional NMR imaging. Electrical forepaw stimulation was performed in Wistar rats anesthetized with ␣-chloralose. SEPs were recorded with calomel electrodes at stimulation frequencies of 1.5, 3, 4.5, and 6 Hz. At the same time, T* 2-weighted imaging was performed, and the signal intensity increase during stimulation was correlated with the mean amplitude of the SEP. Both the stimulation-evoked signal intensity increase in T* 2-weighted images and the amplitude of SEPs were dependent on the stimulation frequency, with the largest signals at a stimulation frequency of 1.5 Hz and decreasing activations with increasing frequencies. The feasibility of simultaneous, artifact-free recordings of T* 2-weighted NMR images and of evoked potentials is proved. Furthermore, the study demonstrates-in the intact brain-the validity of functional magnetic resonance imaging for estimating the intensity of electrocortical activation. Magn Reson Med 41:469-473