Mouse Models

Mouse models of vasospasm are similar to rat models and have been recently developed to take advantage of transgenic technology. The first model used endovascular perforation of the ACA (122). In this model, a 5-0 monofilament suture with a blunt end is advanced through the ICA up to the ACA until resistance is felt. The suture is advanced 5 mm further to perforate the ACA and then withdrawn. Acute mortality with this model is 28%. To determine vasospasm, animals are perfused with 10% formalin, followed by carbon mixed with 10% gelatin. The diameter of the MCA is then measured under a microscope. Peak vasospasm in this model occurs on day 3 and results in an approximately 20% decrease in MCA diameter compared to

Figure 4 Mouse model of subarachnoid hemorrhage (SAH). (Left) Vasospasm determined after India ink injection. (Right) Evolution of the subarachnoid clot over time. Source: From Ref. 123.

controls. Studies performed with this model were designed to test the potential protective effect of overexpressed superoxide dismutase in transgenic mice.

Advantages of this model include a relatively low cost and the ability to use transgenic mice. Disadvantages include a high mortality rate, moderate vasospasm, lack of standardization of hemorrhagic volume, and interobserver variability when measuring MCA diameters.

A modified technique for intracisternal injection has been reported (123) in which the femoral artery is cannulated and 60 mL of blood is withdrawn and reinjected into the cisterna magna. This technique carries a mortality of approximately 3%; acute (6-12 hr) and chronic (1-3 days) vasospasm are observed after transthoracic perfusion with 10% gelatin and 10% India ink (Fig. 4). The diameters of the basilar artery, ACA, and MCA are measured using a digital camera and stereomicroscope. A histopathologic analysis of cross-sections of the analyzed vessels in the current study showed arterial wall changes consistent with those seen in other models. This model appears to be reproducible, accessible, and comparable to other murine models, and it has the advantage of lower mortality. Disadvantages include mild-to-moderate sustained vasospasm with peaks at 3 days in the ACA (21%) and at 1.5 days in the MCA (15%) and basilar artery (15%).

OTHER MODELS Pig Models

A porcine model of vasospasm in pigs was developed that consists of placement of a catheter into the prepontine cistern, followed by two 12-ml injections of blood, with a 48-hr interval (124). Vasospasm was determined by angiography 48 hr after the first injection in 4 out of the 6 animals studied. Arterial injury was observed in specimens collected between 7 and 24 days after the initial hemorrhage. Pigs were selected due to their tendency to develop spontaneous atherosclerosis with age.

A model that followed a clot placement technique via frontotemporal craniotomy was developed to determine the ability of specific blood fractions that contain hemoglobin to induce morphometric vasospasm of the MCA 10 days after hemorrhage (125). In this study, the fractions that contained hemoglobin induced morphometric vasospasm and ultrastructural changes that were comparable to those observed in the MCA of animals exposed to whole blood.

Goat Models

Blood was injected into the basal cisterns of goats through a parietotemporal catheter to study the role of endothelin-1 in posthemorrhagic vasospasm and to test the ability of nicardipine to prevent SAH and endothelin-1-induced vasospasm (126). The authors reported a decrease of 28% in CBF at 3 days after hemorrhage that resolved by day 7.

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