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      Middle Cerebral Artery Occlusion in Rats : A Neurological and Pathological Evaluation of a Reproducible Model

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          Abstract

          Middle cerebral artery occlusion (MCAO) in rats produces an infarct of varying size. We examined three factors that may influence this variability: animal weight, vascular anatomy, and extent of occlusion in rats undergoing MCAO. We also developed a four-point neurological evaluation scale and validated its usefulness by comparing it with a four-grade pathological determination of the size of the infarct. Of 82 animals subjected to a standard MCAO, 34 developed small cortical infarcts (pathological grades I-II; infarct size less than 25 mm2, 6-17% of the ipsilateral cortex surface area), and 48 large infarcts (pathological grades III-IV, infarct size greater than 25 mm2, 20-56% of surface area). We were able to predict the size of infarction from the neurological evaluation in 83% of the animals, and this accuracy reached 91% when grades I and II and III and IV were considered together (P less than 0.001). In 41 animals subjected to a more extensive vascular occlusion, 89% exhibited large infarcts. Four vascular patterns were identified but none played a significant role in the incidence or size of the cortical stroke. However, rats weighing less than 300 g showed a smaller lesion size than did rats greater than 300 g. Our proposed new MCAO technique appears useful in reproducing large-sized infarcts of the frontoparietal cortex.

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          Rodent models of cerebral ischemia.

          The use of physiologically regulated, reproducible animal models is crucial to the study of ischemic brain injury--both the mechanisms governing its occurrence and potential therapeutic strategies. Several laboratory rodent species (notably rats and gerbils), which are readily available at relatively low cost, are highly suitable for the investigation of cerebral ischemia and have been widely employed for this purpose. We critically examine and summarize several rodent models of transient global ischemia, resulting in selective neuronal injury within vulnerable brain regions, and focal ischemia, typically giving rise to localized brain infarction. We explore the utility of individual models and emphasize the necessity for meticulous experimental control of those variables that modulate the severity of ischemic brain injury.
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            The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age.

            Focal cerebral ischemia was induced by occlusion of the middle cerebral artery in rats. The volumetric assessment of infarcted tissue, 2 days following occlusion, was calculated from the examination of eight preselected coronal sections. Five differing rat strains were examined. A small and variable infarcted volume was seen in Wistar-Kyoto rats; Sprague-Dawley rats had a relatively large, but still variable, infarcted volume. Of the normotensive rat strains, the most reproducible volume of infarcted tissue was seen in Fischer-344 rats; also the absolute value of the infarcted volume did not vary from one series to another in this strain. Chronic arterial hypertension, studied in both normal and stroke-prone spontaneously hypertensive rats, was associated with significantly larger infarction volumes. Age does not change the volume of necrosis: Fischer-344 rats were studied at 3, 9, and 20 months of age, and no significant differences were noted between these ages. Experimental diabetes was induced by the administration of streptozotocin 3 days prior to middle cerebral artery occlusion. Severe hyperglycemia (greater than 400 mg/dl) was associated with a considerably increased volume of infarction. The variability of the resultant lesion is high in the most commonly studied strains, but our results suggest that, for studies in normotensive rats, the use of the Fischer-344 strain produces a standardized and repeatable infarction that may be significantly modified by experimental interventions. Age is not a factor that affects the occlusion-induced infarction; in contrast, both chronic arterial hypertension and experimental diabetes aggravate the histological consequences of middle cerebral artery occlusion in the rat. We conclude that quantitative histological evaluation of infarct size allows a meaningful assessment of the gravity of focal cerebral ischemia.
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              Dorsal cerebral arterial collaterals of the rat.

              This study demonstrated that distal branches of the anterior cerebral artery (ACA) are joined by interarterial anastomoses to rami of the middle cerebral artery (MCA) in the normal Wistar rat. Arteries of 36- and 56-day-old animals were dilated with papaverine and injected with Vultex. Vultex arrived at corresponding ACA and MCA collaterals simultaneously as determined by microscopy through a skull window and photography. There were about 29 ACA-MCA junctions per hemisphere. Junction density was nearly constant along the frontal-occipital axis. The anastomoses were most numerous between 2 and 3 mm lateral to the midline and were less than 120 micron in internal diameter. No significant difference was found between total numbers of junctions for right versus left hemispheres or between age groups. The most evident collateral pattern was characterized by two ACA end rami joining two MCA end branches to form a closed, diamond-shaped collateral unit. Considerations were given to alternate routes of blood flow into the MCA tissue field. We conclude abundant dorsal anastomoses exist in 36- and 56-day-old rats and are the prime potential source for ACA collateral supply to the MCA tissue field.
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                Author and article information

                Journal
                Neurosurgery
                Neurosurgery
                Ovid Technologies (Wolters Kluwer Health)
                0148-396X
                1992
                July 1992
                : 31
                : 1
                : 100-107
                Article
                10.1227/00006123-199207000-00014
                1641086
                1c3d9e86-79a9-45ce-9183-67b68a7f2849
                © 1992
                History

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