An animal model of cerebral infarction. Homologous blood clot emboli in rats.

Abstract

SUMMARY An experimental model of cerebral infarction is created in rats by intracarotid injection of their homologous blood clots. This is the first small animal model in which embolization was achieved by homologous blood clots. The infarcts were produced predominantly in the territory of the middle cerebral artery. The low mortality rate and excellent reproduction rate make possible the correlative study of morphological, biochemical, and metabolic parameters at selected points in time to reconstruct the pathogenesis and natural history of focal cerebral ischemia and its relation to blood elements. Stroke, Vol 13, No 4, 1982 HILL ET AL 1 WERE THE FIRST to use the injection method of homologous blood clots into the carotid artery as an experimental model for cerebral infarction in dogs. This model proved to be very similar to human cerebral infarction but it was difficult to assess the extent and outcome of different parameters. Furthermore, the cost is prohibitive to use dogs in large scale studies. We therefore used rats as an experimental animal and understood that the injection of homologous blood clots into the carotid artery was by far the best method to produce reliable and reproducible infarcts in rat brain in our experimental design. Our results are described to demonstrate its usefulness in the study of cerebral infarction. Material and Method Preparation of Blood Clot EmboliSixty Wistar strain male rats, weighing between 200 and 300 gm, were used. The animals were anesthetized with ether, and 0.1 ml of blood was obtained by cardiac puncture with a tuberculin syringe and stored at room temperature for 48 hours for clot formation. The clot was separated from the serum and was fragmented by injecting it through a 26 gauge needle into normal saline. The latter step was repeated three times. A 0.2 ml clot suspension with fragments of varying sizes but no more than 100 /x was used for the embolization. Procedures of EmbolizationThe animals were again anesthetized with ether. The bifurcation of the left common carotid artery, and the internal and external arteries were surgically exposed. The vagus nerve and sympathetic plexus remained intact. A temporary clip was applied around the external carotid artery just above its origin. A thread was placed around the common carotid artery about 15 mm below the bifurcation. Employing a 26 gauge needle, the emboli suspended in the saline were injected into the common carotid artery distal to the occluded site. At injection, the common carotid artery was temporarily occluded by a gentle lifting of the thread to provide an angle for the easy insertion. Following a smooth and gentle injection, the needle was drawn out and the site of injection was sealed off with surgical adhesive. The clip of the external carotid artery was removed. The thread around the common carotid artery was removed and the flow was established. The surgical site was closed. For control studies, a sham operation was performed in ten animals consisting of either a permanent ligation of the left ...

A Novel Embolic Model of Cerebral Infarction and Evaluation of Stachybotrys microspora Triprenyl Phenol-7 (SMTP-7), a Novel Fungal Triprenyl Phenol Metabolite

“…Clinical manifestations were improved in most animals by 48 h after embolization, but the infarction area was observed until 120 h later. A previous report also showed that clinical signs were much improved by the 5th day after embolization (9). The reason for this discrepancy is not clear from the present study.…”

“…This model is distinct from other blood clot embolic models in terms of the induction of ischemia. The blood clot embolic models previously reported are induced by injection of clots through the common carotid artery (9) or through a catheter attached to the external carotid artery (10). Although these models are closer than suture models to what actually happens in patients with stroke, they exhibit problems of non-uniformity in the infarction area and technical difficulties.…”

Mouse Model of In Situ Thromboembolic Stroke and Reperfusion

“…Although there is a high probability that the MCA is the recipient of emboli, the location of infarcts in these models is not reproducible. 11 This difficulty was overcome by a local delivery of an intact fibrin-rich embolus into the segment of the ICA near the origin of the MCA. 12 Similar strategies were developed in mice by using injection of microemboli.…”

“…9,10 Other workers have used a second type of model involving injection of autologous or heterologous preformed fibrin, blood clots, 11,12,13 including microemboli, 14 or in situ clot formation by using rose Bengal. 15,16 Although these last models are closer to what happens in patients with stroke, they lack reproducibility and uniformity in the resulting infarct volume, the location of the lesion, 17,18 and/or display a high degree of mortality 19 rendering the statistical analysis of the data confusing (for review, 20 ).…”

Hemorrhagic Transformation After Fibrinolysis With Tissue Plasminogen Activator

“…Rats were anesthetized with 1.5% halothane under spontaneous respiration. Subsequent procedures for thromboembolic stroke were performed according to the methods described by Kudo et al, 12 with some added modifications. 6 The donor rat was anesthetized, and the femoral artery was catheterized with a 24-gauge elastic needle.…”