[Mechanisms for the development of intracranial hemorrhage. Possible implications for thrombolysis in cerebral infarct].
The role of cerebral hemorrhagic transformation, either as clinically silent hemorrhagic infarction or disastrous parenchymal hemorrhage, is crucial for any risk/benefit analysis of thrombolysis. Especially, thrombolysis in acute ischemic stroke increases the risk of severe, life-threatening hemorrhagic complications up to 10 times compared to untreated controls. In this paper, previous proposed concepts for the development of intracerebral hemorrhage and hemorrhagic transformation are presented. The role of the cerebral microvasculature will be emphasized. In experimental focal cerebral ischemia a significant loss of basal lamina components of the cerebral microvessels has been demonstrated. This loss in vessel wall integrity is associated with the development of petechial hemorrhage. The mechanisms for this microvascular damage may include the plasmin-generated laminin degradation, matrix metalloproteinases activation, and the transmigration of leukocytes through the vessel wall. The attenuation of the microvascular integrity loss with subsequent reduction in hemorrhage is theoretically possible 1) by an improvement in the definition of an individual time window of therapy (by means of imaging techniques), 2) by a biochemical quantification of the basal lamina damage to avoid dangerous interventions, and 3) by pharmacological strategies to protect the basal lamina during thrombolysis.
Hamann
G F
GF
Neurologische Klinik, Ludwig-Maximilians Universität, Klinikum Grosshadern, München.
del Zoppo
G J
GJ
von Kummer
R
R
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D003952:Diagnostic Imaging; D006801:Humans; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D011379:Prognosis; D015912:Thrombolytic Therapy