Apoptosis in Cerebral Vasospasm After Subarachnoid Hemorrhage

Summary

We hypothesize that the mechanism of cerebral vasospasm after subarachnoid hemorrhage may not be a delayed and prolonged vascular response to certain spasmogens but a more complicated cascade, including contraction, cell death, and proliferation. This study was undertaken to demonstrate the apoptotic cell death induced by oxyhemoglobin in cultured endothelial cells in vitro, apoptosis in endothelium in vivo in a canine double hemorrhage model of experimental subarachnoid hemorrhage, and apoptosis in cerebral endothelial cells in a patient who died of cerebral vasospasm. (1) Oxyhemoglobin-produced endothelial apoptotic cell was demonstrated by apoptotic bodies [transmission electron microscopy (TEM)] and DNA ladders. (2) Endothelial cell damage and detachment were observed in dog middle cerebral arteries 5 days after blood injection. (3) In a patient who died 20 days after aneurysmal subarachnoid hemorrahge, endothelial detachment and apoptotic endothelial cells were demonstrated by TEM and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) reaction. These studies demonstrated that apoptosis may be an important step in vasospasm development. They opened a new avenue for treatment of vasospasm.