In vivo animal models of cerebral vasospasm: a review

Cerebral vasospasm is delayed-onset cerebral arterial narrowing in response to blood clots left in the subarachnoid space after spontaneous aneurysmal subarachnoid hemorrhage (SAH). Ideally, studies on the pathogenesis and treatment of cerebral vasospasm in humans should be conducted using human cerebral arteries. Because in vivo experiments using human vessels are not possible, and postmortem pathological examination of human arteries in vasospasm provides only a limited amount of information, a number of animal models of vasospasm have been developed.

The literature was searched to find all references to in vivo animal models of SAH and vasospasm. An online search of the medical database MEDLINE was initially performed using the key words "cerebral," "vasospasm," "subarachnoid," "hemorrhage," "animal," and "model." References were checked to determine the first description of each in vivo animal model.

Fifty-seven models of SAH and vasospasm were identified. These models used one of three techniques to simulate SAH: 1) an artery was punctured allowing blood to escape and collect around the artery and its neighbors; 2) an artery was surgically exposed, and autologous blood obtained from another site was placed around the artery; or 3) blood from another site was injected into the subarachnoid space and was allowed to collect around arteries. Each technique has advantages and disadvantages. The majority of animal models of SAH and vasospasm use intracranial arteries; however, extracranial arteries have also been used recently in vasospasm experiments. These studies seem easier and less costly to perform, but concerns exist regarding the physiological dissimilarity between systemic and cerebral arteries.

The model of SAH and vasospasm used most frequently is the canine "two-hemorrhage" model, in which two injections of blood into the dog's basal cistern performed 48 hours apart result in greater arterial vasoconstriction than that effected by a single injection of blood. On the basis of its ability to accurately predict what occurs in human SAH, the best model of vasospasm seems to be the primate model in which a blood clot is surgically placed around the large cerebral vessels at the base of the monkey's brain.