Propofol improved neurobehavioral outcome of cerebral ischemia-reperfusion rats by regulating Bcl-2 and Bax expression.

Propofol is an intravenous anesthetic with neuroprotective effects against cerebral ischemia-reperfusion (I/R) injury. Few studies regarding the neuroprotective and neurobehavioral effects of propofol have been conducted, and the underlying mechanisms are still unclear. Because I/R may result in neuronal apoptosis, the apoptosis regulatory genes B-cell leukemia-2 (Bcl-2) and Bcl-2-associated X protein (Bax) may be involved in the neuroprotective process. In this study, 120 Wistar rats were randomly divided into three groups (sham, I/R-induced, and propofol-treated). Cerebral ischemia was induced by clamping the bilateral common carotid arteries for 10min. Propofol (1.0mg/kg/min) was administered intravenously for 1h before the induction of ischemia. Neuronal damage was evaluated by neurobehavioral scores and histological examination of the brain sections at the level of the dorsal hippocampus at 6h, 24h, 48h, 72h, 4days, 5days, 6days, and 7days after I/R. The apoptotic rate of hippocampal neurons was detected by flow cytometry. The expression of Bcl-2 and Bax was evaluated using immunohistochemical and Western blot methods. The results of this study showed that neurobehavioral scores were higher in propofol-treated rats compared with I/R-induced rats with no propofol treatment. Moreover, the hippocampal expression of Bcl-2 was significantly higher, while the expression of Bax was significantly lower in propofol-treated rats compared with I/R-induced rats at 24h after ischemia. Hence, this study suggests that the neuroprotective effects of propofol against neuronal apoptosis may be a consequence of the regulation of Bcl-2 and Bax.

Propofol inhibited the delayed rectifier potassium current (I(k)) via activation of protein kinase C epsilon in rat parietal cortical neurons.

Propofol has been shown to exert neuroprotective effects. Delayed rectifier potassium current (I(K)) was reported to be closely related to neuronal damage. This study was designed to test the effects of propofol on I(K) in rat parietal cortical neurons and the involvement of PKC in this activity. Whole-cell patch-clamp recordings were performed in rat parietal cortical neurons. The amplitudes of I(K) were recorded before and after the addition of different concentrations of propofol. Propofol concentration-dependently inhibited I(K) with an IC50 value of 36.3±2.7 µM. Moreover, propofol caused a downward shift of the I-V curve of I(K) in a concentration dependent manner. The kinetics of I(K) was altered by propofol, with decreased activation and delayed recovery of I(K). Pretreatment with calphostin-C (a non-selective inhibitor of PKC) or PKC epsilon translocation inhibitor peptide (PKC epsilon inhibitor) abrogated the inhibition of I(K) by propofol. In conclusion, propofol inhibited I(K) via the activation of PKC epsilon in rat cerebral parietal cortical neurons.