Mechanisms of angiogenesis in microcirculation of cerebral hemispheres after subarachnoid hemorrhage (SAH) in rats.

J. Josko, S. Hendryk, H. Jedrzejowska-Szypulka, J. Slowinski, B. Gwózdz, K. Zwirska-Korczala.

Department of Physiology, Silesian University School of Medicine, Zabrze, Poland

Subarachnoid hemorrhage (SAH) frequently leads to prolonged cerebral vasospasm resulting in vascular pathology due to endothelial cell ischemia and neuronal hypoxia. Posthemorrhagic vasospasm can be reversed by the administration of phosphoramidon, an endothelin converting enzyme (ECE) blocker, or BQ-123, an endothelin receptor (ETA) blocker. AIM. The aim of the study was to establish whether prolonged vasospasm and endothelial cell hypoxia stimulate angiogenesis in the central nervous system after subarachnoid hemorrhage. Investigations were also performed to determine whether the administration of phosphoramidon or BQ-123 suppresses angiogenesis. METHODS. Experiments were carried out in male Wistar rats injected phosphoramidon or BQ-123 into the cisterna magna following the induction of subarachnoid hemorrhage. The brains were removed 48 h after the hemorrhage for histopathological examinations. Vascular surface density was measured in cerebral hemisphere sections (at the level of the dorsal part of the hippocampus) and brainstem sections (1/2 of the pons). Statistical analysis was performed using nonparametric Wilcoxon test (p < 0.05). RESULTS. An increase in angiogenesis was observed after SAH in cerebral hemispheres but not in brainstem compared to control values. The administration of phosphoramidon or BQ – 123 was found to inhibit angiogenesis in cerebral hemispheres. CONCLUSIONS. The results obtained have shown a close correlation between endothelial hypoxia in cerebral microvessels and enhanced angiogenesis after subarachnoid hemorrhage.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Angiogenesis.