scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Transorbital Approach to the Middle Cerebral Artery of the Squirrel Monkey: A Technique for Experimental Cerebral Infarction Applicable to Ultrastructural Studies

01 Mar 1970-Stroke (Lippincott Williams & Wilkins)-Vol. 1, Iss: 2, pp 107-111
TL;DR: Modifications to a previously devised method for induction of cerebral infarct are herein described and this new surgical approach has made it possible to conduct detailed and sequential ultrastructural analysis of experimental cerebralinfarctions.
Abstract: An appropriate surgical technique for the production of cerebral infarction must fulfill, among others, the following criteria in order to be suitable for electron microscopy (EM) studies: (1) the method of arterial occlusion should yield a high percentage of infarcts with predictable average size; (2) there must be avoidance of surgical manipulation (i.e., retraction) of the cerebral tissues or exposure of the same to the atmosphere; and (3) the method for occluding the artery must be one that permits fixation by perfusion of the ischemic and nonischemic brain. Modifications to a previously devised method for induction of cerebral infarct are herein described. This new surgical approach has made it possible to conduct detailed and sequential ultrastructural analysis of experimental cerebral infarctions.
Citations
More filters
Journal ArticleDOI
TL;DR: The ability to produce a consistent focal ischaemic lesion in the rodent brain provides a technical approach that is sufficiently reproducible to enable investigation of the pathophysiology of ischaemia using recently developed autoradiographic and neurochemical methods.
Abstract: Summary: A procedure for occluding the stem of the proximal middle cerebral artery of the rat is described. The operation is performed under anaesthesia through a small subtemporal craniectomy. After occlusion, 3 animals were perfused with carbon black and 8 with a FAM fixative (40% formaldehyde, glacial acetic acid, and methanol). The findings were compared with sham-operated animals. Carbon black studies demonstrated an area of impaired perfusion corresponding to the territory of the occluded artery in each animal. Neuropathological studies invariably showed that there was ischaemic brain damage in the cortex and basal ganglia. The frontal cortex was involved in every animal, as was the lateral part of the neostriatum; the sensorimotor and auditory cortex were involved in most animals, whereas the occipital cortex and medial striatum were involved only infrequently. The damage produced by ischaemia could be readily distinguished from the small local lesion seen at the surgical site in sham-operated animals. The ability to produce a consistent focal ischaemic lesion in the rodent brain provides a technical approach that is sufficiently reproducible to enable investigation of the pathophysiology of ischaemia using recently developed autoradiographic and neurochemical methods.

1,426 citations


Cites background from "Transorbital Approach to the Middle..."

  • ...The occlusion of an intracranial artery, usually the proximal middle cerebral artery, is widely used to produce focal ischaemia in larger animals such as the cat (Sundt and Waltz, 1966), dog (Suzuki et aI., 1980), and primate (Hudgins and Garcia, 1970)....

    [...]

Journal ArticleDOI
TL;DR: Various rodent animal models, pathogenic mechanisms, and promising therapeutic approaches of ischemic stroke are focused on.
Abstract: Ischemic stroke is a devastating disease with a complex pathophysiology. Animal modeling of ischemic stroke serves as an indispensable tool first to investigate mechanisms of ischemic cerebral injury, secondly to develop novel antiischemic regimens. Most of the stroke models are carried on rodents. Each model has its particular strengths and weaknesses. Mimicking all aspects of human stroke in one animal model is not possible since ischemic stroke is itself a very heterogeneous disorder. Experimental ischemic stroke models contribute to our understanding of the events occurring in ischemic and reperfused brain. Major approaches developed to treat acute ischemic stroke fall into two categories, thrombolysis and neuroprotection. Trials aimed to evaluate effectiveness of recombinant tissue-type plasminogen activator in longer time windows with finer selection of patients based on magnetic resonance imaging tools and trials of novel recanalization methods are ongoing. Despite the failure of most neuroprotective drugs during the last two decades, there are good chances to soon have effective neuroprotectives with the help of improved preclinical testing and clinical trial design. In this article, we focus on various rodent animal models, pathogenic mechanisms, and promising therapeutic approaches of ischemic stroke.

677 citations

Journal ArticleDOI
01 Aug 1989-Stroke
TL;DR: A new focal ischemia model consisting of unilateral middle cerebral artery occlusion with a silicone rubber cylinder attached to a nylon surgical thread inserted through the internal carotid artery in rats that should be useful in various investigations of the influence of reperfusion on focal ischemic brain injury.
Abstract: We describe a new focal ischemia model consisting of unilateral middle cerebral artery occlusion with a silicone rubber cylinder attached to a nylon surgical thread inserted through the internal carotid artery in rats. Recirculation was accomplished by pulling the thread out of the artery. We evaluated the reliability of this model and studied the influence of reperfusion of the brain by measuring regional cerebral blood flow in 30 rats and by using conventional neuropathologic methods after different periods of occlusion in 48 rats. The anterior neocortex and the lateral part of the caudate putamen, which were supplied by the occluded middle cerebral artery, were the regions most frequently damaged. After 1 hour of occlusion in five rats, in the cortex supplied by the occluded artery mean +/- SD blood flow was 0.19 +/- 0.08 ml/g/min (approximately 15% of that in the corresponding region of five sham-operated control rats), and mild scattered ischemic cell change was observed. Three (n = 5) or six (n = 5) hours of occlusion reduced blood flow more severely and caused severe ischemic cell changes in the cortex supplied by the occluded artery in proportion to the duration of ischemia. Characteristically, in five rats subjected to 3 hours of occlusion followed by 3 hours of recirculation, blood flow was restored and spongy edematous change was observed in the cortex supplied by the recirculated artery. This change resulted in hypoperfusion of the neighboring cortical region surrounding the recirculated area. Our model should be useful in various investigations of the influence of reperfusion on focal ischemic brain injury.

542 citations

Journal ArticleDOI
TL;DR: The proposed new MCAO technique appears useful in reproducing large-sized infarcts of the frontoparietal cortex in rats and is able to predict the size of infarction from the neurological evaluation in 83% of the animals.
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.

336 citations

Journal ArticleDOI
TL;DR: The volumetric assessment allows an objective assessment of drug therapy and management strategies in the treatment of cerebral infarction and can readily detect the increase in amount of structural damage in cerebral cortex following a transient episode of hypotension.
Abstract: A method for the volumetric assessment of early cerebral infarction, together with its statistical and biological validation, is described. In halothane anaesthetised rats the stem of the right middle cerebral artery was occluded and 3 hours later (with full monitoring of respiratory and cardiovascular status) the animals were killed by perfusion fixation. In normotensive normocapnic animals the volume of infarction was 52 +/- 4 mm3 in the cerebral cortex and 21 +/- 1 mm3 in the corpus striatum. The reproducibility of the volumetric assessment was found to be excellent (coefficient of correlation 0.995 on 18 replicate measurements). The minimum number of stereotactic levels which must be assessed to yield accurate volumetric measurements of infarction is 8. The method is sensitive at detecting alterations in the amount of infarction. For example, it can readily detect the increase in amount of structural damage in cerebral cortex following a transient episode of hypotension. This approach allows an objective assessment of drug therapy and management strategies in the treatment of cerebral infarction.

310 citations

References
More filters
Journal ArticleDOI
TL;DR: The present study was undertaken to analyze factors influencing the efficiency of the cerebral collateral circulation as measured by means of the polarographic technic, to clarify the circumstances whereby collateral blood flow fails to prevent infarction, and to determine whether any aspects ofinfarction are reversible.
Abstract: CLINICAL INVESTIGATION of syndromes due to atherosclerotic occlusion or stenosis of the internal carotid, middle cerebral, and basilar arteries has shown that many of the transient symptoms characteristic of such disorders are due to temporary failure of the cerebral collateral circulation. In a recent paper on this subject,' cerebrovascular insufficiency was defined as a state where the local or general blood flow was unable to maintain the metabolic requirements of the brain during physiologic stresses. Examples of stress situations commonly producing symptoms are reduction of cardiac output due to blood loss, postural hypotension, and cardiac dysrhythmia. The syndrome of cerebrovascular insufficiency was considered to be due to a discrepancy between supply of arterial blood and tissue demand for oxygen. It is apparent that measures which tend to promote the development of the cerebral collateral circulation following occlusion of a cerebral vessel are of considerable therapeutic importance. The present study was undertaken to analyze factors influencing the efficiency of the cerebral collateral circulation as measured by means of the polarographic technic, to clarify the circumstances whereby collateral blood flow fails to prevent infarction, and to determine whether any aspects of infarction are reversible. Experimental studies with the polarographic technic in monkey cortex24 and later in man5 have demonstrated the high oxygen consumption and small oxygen reservoir of healthy cerebral tissue. Early consequences of cerebral isschemia appear to be due to local hypoxic damage to neurons,3-6 which may be reversible if a minimal blood flow is preserved. Cerebral anoxia results first in slowing of the electroencephalogram and later in an injury potential (S.P. shift). Once neuronal injury has occurred, the tissue demand for oxygen is greatly reduced, since metabolically paralyzed or infarcted brain has a minimal oxygen consump-

188 citations

Journal ArticleDOI
TL;DR: Clinical and experimental evidence indicates that after a delay such treatment may result in recanalization of a thrombosed vessel, and this type of treatment improves transient symptoms due to intermittent ischemia, and decreases the occurrence of cerebral embolism andThrombosis but does not alter the course of cerebral infarction once established.
Abstract: RECENT clinical reports have stressed beneficial effects resulting from the use of anticoagulant drugs in thrombosis of the basilar and carotid arteries1 2 3 4 and in thromboembolic cerebrovascular disease.5 , 6 It was concluded that this type of treatment improves transient symptoms due to intermittent ischemia, decreases the occurrence of cerebral embolism and thrombosis but does not alter the course of cerebral infarction once established.7 How anticoagulant drugs cause benefit in cerebrovascular disease is not fully understood. Clinical and experimental evidence indicates that after a delay such treatment may result in recanalization of a thrombosed vessel. More rapid improvement occurring within the first week . . .

70 citations