Improved rat model for cerebral vasospasm studies

Abstract

While the rat has been used extensively in subarachnoid hemorrhage (SAH)-cerebral vasospasm studies, concerns exist whether this animal represents a usable model because its time course and pattern of cerebral vasospasm following SAH is not comparable to that observed in man. At present, our knowledge of the rat model is based almost exclusively on studies using a 'single hemorrhage' method. Since there is a positive correlation between severity of cerebral vasospasm, and volume of subarachnoid blood, an obvious question is whether the rat will show modifications in vascular responses when insulted by a second SAH. Here, an SAH was produced in rats using a 'double hemorrhage' method. Following SAH, cerebral arteries showed pathological alterations, significant decreases in luminal perimeter, and increases in arterial wall thickness, over a 7-day post-SAH period. The above vascular features are considered to be indicative of cerebral vasospasm and their presence over a 7-day post-SAH period represents a significant time extension when compared to a single hemorrhage. These modified vascular responses made the double hemorrhaged rat a much-improved animal model.

Comparison of three rat models of cerebral vasospasm

“…The induction of subarachnoid hemorrhage using a double blood injection, the double-hemorrhage model, was caused by repeating a second blood injection 48 h after the first induction of subarachnoid hemorrhage using the same method (30,44).…”

“…A substantial number of studies on subarachnoid hemorrhage-induced cerebral vasospasm have been conducted. They used various species and various methods of inducing experimental subarachnoid hemorrhage such as intracisternal administration of blood (12,19,30,38,39,(43)(44)(45)(46), endovascularly (5,11,22,28,38,44,47) or extravascularly (4,20) puncturing the artery, and blood clot placement around the artery (15). It can be said that existing subarachnoid hemorrhage models of large animals, such as primates and canines, are the preferred models for cerebral vasospasm (31); however, these preferred models are high in cost and often limited in availability due to the difficulties involved in extensive surgery and handling of the subjects when inducing subarachnoid hemorrhage.…”

“…It can be said that existing subarachnoid hemorrhage models of large animals, such as primates and canines, are the preferred models for cerebral vasospasm (31); however, these preferred models are high in cost and often limited in availability due to the difficulties involved in extensive surgery and handling of the subjects when inducing subarachnoid hemorrhage. In recent years, rats have become a popular species in the study of cerebral vasospasm for the following reasons: 1) all types of methods used to induce subarachnoid hemorrhage are possible in rats; 2) cerebral vasospasm after subarachnoid hemorrhage in rat species show biphasic patterns with early and late phases (12,30,44), as found in humans (24); 3) rat models display pathological alterations in major cerebral arteries (11,19,30) similar to that of humans (34); 4) it is possible to monitor physiological parameters such as mean arterial blood pressure, intracranial pressure, and cerebral blood flow in rats (4,6,20,28,30); 5) more information, such as genetic or genomic, is available in rats than in other large animals (7,18); and 6) rat species also offer additional advantages in that they are available in large numbers, are inexpensive, and are easy to handle and care for.…”

The Effect of Blood Glutamate Scavengers Oxaloacetate and Pyruvate on Neurological Outcome in a Rat Model of Subarachnoid Hemorrhage

“…There are several rat models of SAH, including endovascular perforation of the internal carotid artery [9][10][11], blood injection into pre-chiasmatic cistern [11], and blood injection into the cisterna magna [11][12][13][14][15][16][17]. The last model has 2 modifications: a single hemorrhagic model [16,18] and a double hemorrhagic model [13,19], which are intended to simulate the late complication of vasospasm commonly seen after SAH [13,19].…”

“…The last model has 2 modifications: a single hemorrhagic model [16,18] and a double hemorrhagic model [13,19], which are intended to simulate the late complication of vasospasm commonly seen after SAH [13,19]. All models have their own advantages and disadvantages [11,12,19].…”