Physiological Assessments of Subarachnoid Hemorrhage - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 315

Clinical studies have now shown that SDs occur in abundance
after SAH, both in the early and the late time period. In the fi rst
pilot study of eighteen patients, 72% of patients developed SDs ( 6 ).
Clinical symptoms of DCI were found in seven patients around day
8 after SAH. DCI developed time-locked to a sequence of recur-
rent SDs in every single case. In four of these patients delayed
ischemic strokes evolved in the recording area as assessed by
neuroimaging. These strokes were associated with progressive
prolongation of the electrocorticographic depression periods to
more than 60 min. In a second study of 13 patients, SDs with
prolonged negative DC shifts were identifi ed after SAH ( 8 ). Moreover,
SDs with negative DC shifts of more than 1 h duration were
recently demonstrated in SAH patients similar to SDs that occur in
the core of brain infarcts in animals ( 21 ).
In direct relation to the pathophysiological changes in neurons
during and after SAH, Chap. 23 explain electrophysiological and
imaging tools for the study of SD in animal experiments and
in vitro; Chap. 25 describes microdialysis as a tool for the assessment
of neurometabolic changes in tissue at risk for cellular death; and
Chap. 29 presents techniques for the assessment of hippocampal
function with its selectively vulnerable neuron population.

3. Physiological
Assessments of
the Vascular Side

Traditionally, proximal vasospasm has played the dominant role in
SAH research as it has been accused to cause DCI ( 22 ). However,
it has been increasingly questioned that vasospasm of major cerebral
arteries alone determines delayed brain damage after SAH. Initially,
the large dominance of cortical over territorial infarcts in the patho-
anatomical literature gave rise to this debate ( 23 ). Moreover, only
weak correlations were found between sites/severity of vasospasm
and perfusion changes ( 24, 25 ). Later, the discovery of spreading
ischemia in animal experiments and experimental evidence that
spreading ischemia occurs in response to brain topical application
of erythrocyte degradation products provided a complementary
mechanism for the energy depletion after SAH ( 18, 26 ). Moreover,
it was increasingly discussed that the positive predictive value of
proximal vasospasm is low for DCI or local development of infarcts
( 5, 27 ). Other potential mechanisms of energy depletion, such as
chronic vasospasm in the cortical microcirculation ( 28 ) or the
occurrence of microthrombosis were proposed to cause DCI
( 29, 30 ). Most recently, this controversy gained steam by the
observation that the endothelin A receptor antagonist clazosentan
caused a 65% relative risk reduction of angiographic vasospasm
whereas the patient outcome did not improve signifi cantly ( 31 ).
The current status of knowledge suggests that proximal vasospasm