Physiological Assessments of Subarachnoid Hemorrhage - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 317

The impact of these different phenomena on outcome and the
potential to interfere with a given phenomenon has to be elucidated
in further clinical trials. For the investigation of SD, spreading isch-
emia and BBB disruption after SAH, DISCHARGE-1, a prospective
multicenter study has been started recently ( http://www.controlled-
trials.com/ISCRTN05667702 ; http://www.strokecenter.org/trials/
trialDetail.aspx?tid=1014 ) . Moreover, further animal research will be
necessary for which Chaps. 24 - 26 and 28 describe methodological
tools. Chapter 27 addresses methodological tools for the assessment
of intracranial pressure which has been known as an important
player in SAH pathogenesis for a long time.
It will be a major challenge of the clinical and experimental
studies in the upcoming decade to clarify the question of hen and
egg in this puzzle. For example, experimental evidence suggests
that erythrocyte degradation products covering the cortex can
produce spreading ischemia in response to SD in a similar fashion
to that of conditions in the penumbra after middle cerebral artery
occlusion ( 26, 39, 40 ). Increased excitability can lead up to SD as
much as energy depletion by thromboembolic events or vasospasm
induced by endothelin-1 ( 41-45 ). Spreading ischemia produces a
low-fl ow condition that should promote the occurrence of micro-
thrombosis. It may turn out that the future treatment of SAH
will consist of drug combinations that target different interlaced
pathophysiological mechanisms. This will render clinical intervention
trials even more challenging. However, the novel clinical neuromoni-
toring tools will allow more detailed assessments of the parenchymal
responses to interventions and will hopefully guide us through the
increasing complexity as our knowledge grows.

Acknowledgment

Supported by grants of the Deutsche Forschungsgemeinschaft
(DFG DR 323/3-1, 323/5-1), the Bundesministerium für Bildung
und Forschung (Center for Stroke Research Berlin, 01 EO 0801)
and the Kompetenznetz Schlaganfall to Dr. Dreier.

References

1. Broderick JP, Brott TG, Duldner JE, Tomsick
T, Leach A (1994) Initial and recurrent bleeding
are the major causes of death following subarach-
noid hemorrhage. Stroke 25(7):1342-1347
2. Findlay JM, Deagle GM (1998) Causes of mor-
bidity and mortality following intracranial aneu-
rysm rupture. Can J Neurol Sci 25(3):209-215

3. Roos YB, de Haan RJ, Beenen LF, Groen RJ,
Albrecht KW, Vermeulen M (2000)
Complications and outcome in patients with
aneurysmal subarachnoid haemorrhage: a pro-
spective hospital based cohort study in the
Netherlands. J Neurol Neurosurg Psychiatry
68(3):337-341