Hemorrhagic Transformation of Cerebral Infarction – Possible Mechanisms

Abstract

SummaryTo analyse the risk/benefit of cerebral thrombolysis the role of hemorrhagic transformation, either as clinically silent hemorrhagic infarction or disastreous parenchymal hemorrhage, is crucial. Thrombolysis in acute ischemic stroke increases the risk of severe, life-threatening hemorrhagic complications by up to 10 times compared to 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 plasmin-generated laminin degradation, matrix metalloproteinases activation, transmigration of leukocytes through the vessel wall, and other processes. We propose that 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.

Direct arterial damage and neurovascular unit disruption by mechanical thrombectomy in a rat stroke model

“…In rats, endogenous IgG is distributed in NVU breakdown areas (Richmon et al, 1998), which is related to hemorrhagic complications in ischemic stroke (Hamman, del Zoppo, & von Kummer, 1999). In our study, the observed IgG leakage ( Figure 2) was indicative of NVU damage in the vessels of the infarct area, as well as mechanically injured vessels.…”

Cerebral Hemodynamic Evaluation After Cerebral Recanalization Therapy for Acute Ischemic Stroke

“…Although the safety of poststroke hyperperfusion is controversial, there are concerns that elevated BP and significantly increased CBF velocities may be associated with cerebral hyperperfusion syndrome, characterized by headaches, hemorrhagic transformation, and epileptic seizures (56). A possible mechanism is cerebral vessel wall injuries and vulnerability to the excessive blood flow due to the endovascular operation (Table 2, Figure 1) (57–59). We suggest that physicians pay attention to patients who have received recanalization therapy, particularly mechanical thrombectomy, with blood flow acceleration of >30–40% in the affected arteries compared to the blood flow velocity in the contralateral side determined using TCD, or a 70–80% increase in CBF volume compared with that on the non-infarct side determined by perfusion imaging (39, 40).…”