Assessment of Microthromboembolism After Subarachnoid Hemorrhage - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 369

impaired cerebral autoregulation. Here, we further discuss the
microthromboembolism hypothesis and a method to determine its
presence in experimental models of SAH.
Microthromboembolism was perhaps fi rst described in an
autopsy study of patients by Suzuki et al. ( 1 ). At least as early as the
1960, Ohta et al. ( 2 ) was considering the role of thromboembo-
lism in the pathogenesis of cerebral ischemia and infarction in patients
with aneurismal SAH. Later, the observation of microthromboem-
bolism was confi rmed in other studies ( 3-5 ), and its role in the
pathogenesis of DCI extensively reviewed ( 6 ). It has been shown
that patients who die from DCI have signifi cantly more microthrombi
in clinically ischemic regions and in areas showing cerebral infarction
on computed tomographic scan, when compared with patients who
die from rebleeding or acute hydrocephalus, although the patients
who died from rebleeding died before DCI usually develops ( 7 ).
So far, the association between microthromboembolism and infarction
suffers from all of the same issues regarding causality as the associa-
tion between angiographic vasospasm and infarction.
Microthrombi mostly consist of a combination of fi brin thrombi
and aggregated platelets, eventually mixed with multinuclear
leukocytes. Since microclots are not only present in regions with
clinical signs of DCI or infarction but are widespread in the brain,
an additional factor is apparently necessary for the development of
clinical signs of focal cerebral ischemia. This is supported by the
results of an autopsy study that investigated 29 SAH patients and
showed pathologic evidence of ischemia in 93% patients, but clinical
signs of DCI were present in only 48% of the studied patients ( 5 ).
These data could lead one to hypothesize that microthromboem-
bolism and vasospasm are complementary mechanisms in the
pathogenesis of DCI. Interestingly, not only vasospasm but also
microclot burden is infl uenced by the volume of subarachnoid
blood ( 5 ). In a large autopsy study investigating microthromboem-
bolism in SAH patients, which showed that cortical ischemic lesions
were present in 41 of the 53 patients studied, no signifi cant associa-
tion was observed between the presence of cortical ischemic lesions
and angiographic vasospasm or location of the aneurysm ( 4 ). The
limitations of studying only patients who die at variable times after
SAH, and who undergo angiography in varying numbers, limit
conclusions that can be drawn from such data.
Although microthromboembolism has been described in several
human autopsy studies, no studies are available in the present litera-
ture that describes the assessment of microthromboembolism in
SAH animal models. It is not clear how many of the clots observed
are thrombi and how many are emboli. Therefore, we use the term
microthromboemboli and we here outline some unpublished obser-
vations as well as the materials and procedures that are needed; the
preparation, immunohistochemical staining and assessment of brain
sections, and the quantifi cation and presentation of microthrom-
boembolism.