Endothelin-1 expression and alterations of cerebral microcirculation after experimental subarachnoid hemorrhage

Abstract

Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) often leads to poor outcomes in SAH patients. Overexpression of endothelin-1 (ET-1) could contribute to the development of CVS. The purpose of this study was to investigate cerebral microcirculation by whole-brain perfusion CT scan and ET-1 expression following SAH. SAH was induced in rabbits. Cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and mean transit time (MTT) were measured with CT perfusion techniques at days 1, 4, 7, and 14 following SAH. Expression of ET-1 was determined by ELISA accordingly. Histological sections of the brain tissue were also examined. Whole-brain perfusion showed that CBV and TTP increased at day 4 and maintained elevated rate until day 14. MTT increased at day 4, peaked at day 7, and then decreased at day 14. CBV of the occipital lobe was greater than that in the frontal and parietal lobes at day 4. CBF of the occipital lobe increased significantly compared to that of other lobes at day 7. ET-1 expression in the SAH group was significantly greater than that in the control at various time points. Moreover, ET-1 levels were positively correlated with MTT value. CTP detects changes in cerebral microcirculation following SAH. Microcirculation of each lobe was different and could be quantified to identify high-risk areas of cerebral ischemia. ET-1 expression was significantly increased and was correlated with MTT as well, suggesting that ET-1 influences cerebral microcirculation following SAH.