Effect of HX0507, a water-soluble propofol pro-drug, on subarachnoid hemorrhage-induced cerebral vasospasm in rabbits

摘要

BACKGROUND:Propofol has been shown to attenuate neuronal injury in a number of experimental conditions.However,its effect in models of cerebral ischemia after subarachnoid hemorrhage(SAH) remains controversial. OBJECTIVE:To explore the effects of intracistemal injection of HX0507,a water-soluble propofol prodrug,on basilar artery vasospasm and brain tissue injury in a rabbit model of SAH. DESIGN,TIME AND SETTING:A randomized,controlled,in vivo animal experiment based on behavior and morphology.The study was performed at the Laboratory of Anesthesiology and Critical Care Medicine,West China Hospital,Sichuan University from April to December 2007. MATERIALS:HX0507 was provided by the Laboratory of Anesthesiology and Critical Care Medicine,West China Hospital of Sichuan University. METHODS:A total of 30 healthy,male,New Zealand rabbits were randomly assigned to sham-operation,SAH-control,and SAH-HX0507 groups,with 10 animals in each group.The single-hemorrhage SAH model was established by injecting autologous arterial blood(1.0 mL/kg) into the cisterna magna in the SAH-control and SAH-HX0507 groups,while the sham-operation group was injected with normal saline(1.0 mL/kg).Thirty minutes after injection,the sham-operation and SAH-control groups were injected with normal saline(0.1 mL/kg) into the cisterna magna,while the SAH-HX0507 group received an injection of HX0507(4.8 mg/kg). MAIN OUTCOME MEASURES:The cross-sectional area and corrugation coefficients of basilar arteries and hippocampal CA1 neuronal densities were measured 48 hours after SAH(peak stage of vasospasm) using the Computer-Assisted Stereological Toolbox system.The ultrastructural structure of the basilar artery wall was examined by transmission electron microscopy.In addition, neurological behavioral impairment was evaluated by appetite score at pre-SAH,and 1 and 2 days after SAH. RESULTS:The cross-sectional area of basilar arteries and hippocampal CA1 neuronal densities,as well as ultrastructural structure scores of the SAH-control group were significantly less than the other groups(P0.05). CONCLUSION:Intracisternal administration of HX0507 attenuated basilar artery vasospasm and hippocampal ischemic injury in a rabbit model of SAH.