We have used a photochemical reaction in vivo to induce reproducible thrombosis leading to cerebral infarction in rats. After the intravenous injection of rose bengal, a potent photosensitizing dye, an ischemic lesion was formed by irradiating the left parietal convexity of the exposed skull for 20 minutes with green light (560 nm) from a filtered xenon arc lamp. Animals were allowed to survive from 30 minutes to 15 days after irradiation. Early microscopic alterations within the irradiated zone included the formation of thrombotic plugs and adjacent red blood cell stasis within pial and parenchymal vessels. Scanning electron microscopy revealed frequent platelet aggregates adhering to the vascular endothelium, often resulting in vascular occlusion. Carbon-black brain perfusion demonstrated that occlusion of vascular channels progressed after irradiation and was complete within 4 hours. Histopathological examination at 1, 5, and 15 days revealed that the associated infarct evolved reproducibly through several characteristic stages, including a phase of massive macrophage infiltration. Although cerebral infarction in this model is initiated by thrombosis of small blood vessels, the fact that the main pathological features of stroke are consistently reproduced should permit its use in assessing treatment regimens. Further, the capability of producing infarction in preselected cortical regions may facilitate the study of behavioral, functional, and structural consequences of acute and chronic stroke.

Summary: This study was undertaken to test whether transient depolarizations occurring in periinfarct regions are important in contributing to infarct spread and matu ration. Following middle cerebral artery (MCA) occlusion we stimulated the ischemic penumbra with recurrent waves of spreading depression (SD) and correlated the histopathological changes with the electrophysiological recordings. Halothane-anesthetized, artificially venti lated Sprague-Dawley rats underwent repetitive stimula tion of SD in intact brain (Group 1; n = 8) or photothrom botic MCA occlusion coupled with ipsilateral common carotid artery occlusion (Groups 2 and 3, n = 9 each). The electroencephalogram and direct current (DC) poten tial were recorded for 3 h in the parietal cortex, which represented the periinfarct border zone in ischemic rats. In Group 2, only spontaneously occurring negative DC shifts occurred; in Group 3, the (nonischemic) frontal pole of the ischemic hemisphere was electrically stimu lated to increase the frequency of periinfarct DC shifts. Animals underwent perfusion-fixation 24 h later, and vol umes of complete infarction and scattered neuronal injury ("incomplete infarction") were assessed on stained coro nal sections by quantitative planimetry. Electrical induc tion of SD in Group 1 did not cause morphological injury. During the initial 3 h following MCA occlusion, the num ber of spontaneous periinfarct depolarizations in Group 2 (7.0 ± 1.5 DC shifts) was doubled in Group 3 by frontal

Summary: Hyperglycemia exacerbates neuronal injury in the setting of reversible brain ischemia, but its effect on focal thrombotic infarction has been less extensively characterized. We investigated this problem in two rat models of focal vascular occlusion. In Model I, the right middle cerebral artery (MeA) was exposed via a subtem poral craniotomy in halothane-and nitrous oxide-anes thetized Wistar rats and was occluded photochemically by irradiation with an argon ion laser following the intra venous administration of the photosensitizing dye rose bengal. Permanent MeA occlusion was combined with temporary bilateral common carotid artery ligation. In Model II, similarly anesthetized Sprague-Dawley rats were subjected to permanent photochemical occlusion of the right MeA without common carotid occlusion. In both models, rats were food deprived for 24 h and were administered varying amounts of 50% dextrose (or saline) 15 min prior to vascular occlusion to produce a spectrum of plasma glucose values, ranging from 5 to 44 f.1mollml. Brains were examined histologically 7 days following vascular occlusion, and computer-assisted planimetry was used to compute infarct volumes. In Model I, the volume of neocortical infarction ranged from 30.3 to 108.4 mm3 and exhibited a strong linear correlation withIn the setting of high-grade transient global brain ischemia, it is now generally accepted that elevated plasma glucose levels (in particular, when present prior to an ischemic insult) markedly influence out come (Siemkowicz and Hansen, 1978) and give rise to postischemic energy metabolite depletion Rehncrona et al. , 1981), hypoperfusion 186increasing preischemic plasma glucose values (r = 0.70). In contrast, the size of the smaller striatal infarct in this model was not correlated with plasma glucose level. In Model II, there was a prominent striatal infarct, ranging in volume from 14.4 to 96.4 mm3, while neocortical in farction occurred inconstantly. As in Model I, striatal in farct volume in Model II showed no correlation with plasma glucose level. These results are consistent with the view that infarcted regions having collateral circula tion [neocortex in MeA occlusion (Model I)] are vulner able to the deleterious effects of hyperglycemia, whereas regions of nonanastomosing (end-arterial) vascular supply are not [striatum in Models I and II, and neo cortex in previously reported model of photochemically induced primary microvascular thrombosis (Ginsberg et aI., 1987) J. Thus, the harmful effects of elevated plasma glucose in stroke appear to be complex and may depend critically upon the degree to which collateral perfusion is available to the specific brain regions affected, as well as the extent to which local blood flow is reduced and the timing of glucose administration.

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It has been hypothesized that ischemia, followed by reperfusion, facilitates peroxidative free-radical chain processes in brain. To resolve this question, rats were subjected to reversible global ischemia. From coronal sections of brains frozen in situ, small (ca. 2 mg) amounts of tissue were sampled from neocortex, hippocampus, and thalamus of both cerebral hemispheres of four groups of rats exposed to 30 min cerebral ischemia followed by 0, 30, 60, and 240 min of reperfusion, and from a control group subjected to the same operative procedures, except for the induction of ischemia. Heptane-solubilized total lipid extracts from these samples were analyzed spectroscopically in the 190-330 nm range for content of isolated (nonconjugated) double bonds and of conjugated diene structures; the latter are formed from isolated double bonds during peroxidation of unsaturated fatty acids. Spectra derived from tissue regions of rats subjected to ischemia, or ischemia followed by reperfusion, were compared to averaged, region-specific control spectra and were normalized to the original content of isolated double bonds in the peroxidized samples. The resultant difference spectra were analyzed in terms of ratios of conjugated diene concentration to the concentration of isolated double bonds originally at risk in the specific tissue zones considered. The peak representing conjugated diene formation was centered at 238 +/- 1 nm and was usually well resolved when the molar ratio [conjugated diene]/[isolated double bonds], expressed as a percentage [( CD]/[IDB]), was greater than 0.25%.(ABSTRACT TRUNCATED AT 250 WORDS)