Aneurysmal Subarachnoid Hemorrhage Grading in Animal Models - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 304

Each model has several variations and modifi cations of technique
that all aim to improve on each models effi cacy and reproducibility.
The advantages and disadvantages of each model are the subject of
several reviews ( 3-5 ), and detailed instructions on how to perform
each of these models have been provided previously ( 2 ). The ani-
mals of choice for these models have typically been rats weighing
between 280 and 350 g, mostly due to their low cost in compari-
son to larger rodent, canine, and primate models. The rat also
offers and signifi cantly larger anatomy in comparison to mouse
species 20-25 g, making many of the surgical techniques less chal-
lenging. However, perforation and injection models exist for
smaller (mouse) as well as the larger pig, cat, canine, and primate
species ( 2, 6, 7 ).
The purpose of using animal models is to create pathology that
closely parallels human disease in a consistent manner so that we may
study the pathophysiology and test the effi cacy of potential treat-
ments. One of the most critical steps to this process is the reproduc-
ibility of results, and this requires a stable model that consistently
causes similar injury to each animal. It is only when test animals have
similar degrees of injury we can test the effi cacy of potential treat-
ments. Injection models of aneurysmal subarachnoid hemorrhage
have the advantage of having a known quantity of blood injected
into the subarachnoid space. Injection of a defi ned amount of autol-
ogous blood should allow for highly reproducible results and equiv-
alent hemorrhage volumes among the animals, however, Prunnel
et al. found a high degree of fi nal subarachnoid blood volume in
some injection models ( 5 ). Despite the advantage of hemorrhage
volume reproducibility most injection models offer, they are often
criticized because they do not recreate many of the physiological
aspects of true aneurysmal rupture, such as vessel damage and pro-
longed reductions in cerebral blood fl ow ( 5 ). Additionally, injection
models mandate craniotomy, which may confound the effects of
subarachnoid blood on ICP and cerebral blood fl ow.
On the other hand, endovascular perforation models more
closely mimic true aneurysm rupture pathophysiology, but at the
cost of signifi cant mortality (up to 50%), and high degrees of vari-
ability in hemorrhage size ( 1, 2, 4, 5 ). Without the ability to con-
trol how much hemorrhage is going to result from vascular puncture,
there is no way to know how severe any given animal's injury will
be. This makes it diffi cult, if not impossible, to interpret therapeutic
results. Effective treatments could potentially fail if there was an
unequal distribution of severe injury in treatment groups versus
untreated controls. Additionally, the effi cacy of treatment may not
manifest itself if only the most severe injuries are evaluated. This
could result in the potential benefi ts in the treatment in mild or
moderate injury going unrecognized. In order to overcome these
obstacles, a system for the quantifi cation of injury must be imple-
mented in the study of aneurysmal subarachnoid hemorrhage, in