The Effect Of Propofol On The Pathologic Time-course And Apoptosis After Cerebral Ischemia-reperfusion Injury

Objective: To investigate the effect of propofol on the neurologic deficit, histologic outcome, apoptosis and expression of apoptosis-regulating protein in a series of time-course of focal cerebral ischemia-reperfusion injury in rats. Method: Male SD rats were scheduled to undergo middle cerebral artery occlusion and reperfusion by an intraluminal suture technique. The dose-respone and time-respone effect of propofol was determined through neurologic deficit evaluation and infarct volume image analysis. The morphologic changes of apoptosis under different duration of ischemia were detected by a specialized label technique termed TUNEL staining combined with ultrastructural examination, and the effect of propofol on the time-course development of apoptosis was observed. The expression of anti-apoptotic protein bcl-2 on post-ischemia neuron and the influence of propofol was analyzed by immunochemistry staining. Result: Propofol significantly attenuated neurologic deficit, reduced infarct and edema volumes induced by 3 h ischemia and 24 h reperfusion, when given prior the onset of ischemia, during ischemia or 3 h after reperfusion. This effect was not shown after 3 h post-reperfusion. The result from the observation at the cellular or subcellular level indicated that apoptosis obviously appeared after 6 h reperfusion preceded by 90 min ischemia, rose to the maximum value at 24 h post-reperfusion and gradually diminished after 3 days reperfusion. The peak phase of apoptosis was existed since 6 h to 3 days post-reperfusion and a shift from apoptosis to necrosis occurred after 3 days reperfusion. The time-course of apoptosis was not obviously presented, while necrosis was quickly happened, in the rat model of severe ischemia. Propofol inhibited apoptotic morphologic changes at all post-reperfusion time point and the most significant effect was shown between 6 h to 3 days post-reperfusion. Furthermore, propofol enhanced the expression of anti-apoptotic protein bcl-2 on post-reperfusion neuron and this action was in accordance with the time-course of apoptosis. Conclusion: The pathologic outcome of focal cerebral...