Skip to main content Accessibility help

Sevoflurane and propofol influence the expression of apoptosis-regulating proteins after cerebral ischaemia and reperfusion in rats

  • K. Engelhard (a1), C. Werner (a1), E. Eberspächer (a1), M. Pape (a1), M. Blobner (a1), P. Hutzler (a2) and E. Kochs (a1)...



Background and objective: Sevoflurane and propofol reduce the extent of necrosis and improve neurological outcome in rodent models of cerebral ischaemia and reperfusion. However, the effects of these anaesthetics on programmed cell death (apoptosis) are unclear. The present study investigates whether sevoflurane and propofol affect the expression of apoptosis-regulating proteins after cerebral ischaemia in rats.

Methods: Thirty-two fasted male Sprague–Dawley rats were tracheally intubated and the lungs were ventilated (isoflurane and N2O/O2 anaesthesia). After surgical preparation, the animals were randomly assigned to one of the following groups: control (n = 8): fentanyl intravenous (10 μg kg−1 bolus and 25 μg kg−1 h−1 infusion) with N2O/O2; sevoflurane (n = 8): 2.0% sevoflurane (end-tidal concentration) and O2/air; propofol (n = 8): 0.8–1.0 mg kg−1 min−1 propofol intravenous and O2/air; sham-operated (n = 8): 25 μg kg−1 h−1 fentanyl intravenous and N2O/O2, no cerebral ischaemia. Ischaemia (30 min) was induced by unilateral common carotid artery occlusion plus haemorrhagic hypotension to a mean arterial pressure of 30–35 mmHg. Four hours after cerebral ischaemia the brains were removed and the expression of apoptosis-regulating proteins (Bax, Bcl-2, p53, Mdm-2) was determined using immunofluorescence and Western-blot analyses.

Results: The expression of the pro-apoptotic protein Bax was greater in control animals than in sevoflurane or propofol anaesthetized rats and than in sham-operated animals. The concentrations of Bcl-2, p53 and Mdm-2 were not changed 4 h after cerebral ischaemia.

Conclusions: In addition to the anti-necrotic effects of sevoflurane and propofol, these anaesthetics also reduce the concentration of the apoptosis-inducing protein Bax as early as 4 h after ischaemia.


Corresponding author

Correspondence to: Kristin Engelhard, Klinik für Anaesthesiologie der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Straße 22, München 81675, Germany. E-mail:; Tel: +4989 4140 4291; Fax: +4989 4140 4886


Hide All


Ishimaru MJ, Ikonomidou C, Tenkova TI, et al. Distingushing excitotoxic from apoptotic neurodegeneration in the developing rat brain. J Comp Neurol 1999; 408: 461476.
Biebl M, Cooper CE, Winkler J, Kuhn HG. Analysis of neurogenesis and programmed cell death reveals a self-renewing capacity in the adult rat brain. Neurosci Let 2000; 291: 1720.
Gelb AW, Bayona NA, Wilson JX, Cechetto DF. Propofol anesthesia compared to awake reduces infarct size in rats. Anesthesiology 2002; 96: 11831190.
Warner DS, McFarlane C, Todd MM, Ludwig P, McAllister AM. Sevoflurane and halothane reduce focal ischemic brain damage in the rat. Possible influence on thermoregulation. Anesthesiology 1993; 79: 985992.
Kochs E, Hoffman WE, Werner C, Thomas C, Albrecht RF, Schulte am Esch J. The effect of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. Anesthesiology 1992; 76: 245252.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 1976; 72: 248254.
Werner C, Möllenberg O, Kochs E, Schulte am Esch J. Sevoflurane improves neurological outcome after incomplete cerebral ischaemia in rats. Br J Anaesth 1995; 75: 756760.
Yamasaki T, Nakakimura K, Matsumoto M, Xiong L, Ishikawa T, Sakabe T. Effect of graded suppression of the EEG with propofol on the neurological outcome following incomplete cerebral ischemia in rats. Eur J Anaesthesiol 1999; 16: 320329.
Yamaguchi S, Hamaguchi S, Mishio M, Okuda Y, Kitajima T. Propofol prevents lipid peroxidation following transient forebrain ischemia in gerbils. Can J Anesth 2000; 47: 10251030.
Pittman JE, Sheng H, Pearlstein R, Brinkhous AD, Dexter F, Warner DS. Comparison of the effects of propofol and pentobarbital on neurologic outcome and cerebral infarct size after temporary focal ischemia in the rat. Anesthesiology 1997; 87: 11391144.
Jevtovic-Todorovic V, Wozniak DF, Powell S, Olney JW. Propofol and sodium thiopental protect against MK-801-induced neuronal necrosis in the posterior cingulate/retrosplenial cortex. Brain Res 2001; 913: 185189.
Moe MC, Berg-Johnsen J, Larsen GA, Røste GK, Vinje ML. Sevoflurane reduces synaptic glutamate release in human synaptosomes. J Neurosurg Anesthesiol 2002; 14: 180186.
Cao G, Minami M, Pei W, et al. Intracellular Bax translocation after transient cerebral ischemia: implications for a role of the mitochondrial apoptotic signaling pathway in ischemic neuronal death. J Cereb Blood Flow Metab 2001; 21: 321333.
Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609619.
Miyashita T, Krajewski S, Krajewska M, et al. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 1994; 9: 17991805.
Selvakumaran M, Lin HK, Miyashita T, et al. Immediate early up-regulation of bax expression by p53 but not TGF beta1: a paradigm for distinct apoptotic pathways. Oncogene 1994; 9: 17911798.
Tu Y, Hou S-T, Huang Z, Robertson GS, MacManus JP. Increased Mdm-2 expression in rat brain after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab 1998; 18: 658669.
Wise-Faberowski L, Raizada MK, Summers C. Oxygen and glucose deprivation-induced neuronal apoptosis is attenuated by halothane and isoflurane. Anesth Analg 2001; 93: 12811287.
Kodaka M, Mori T, Tanaka K, Nomura M, Kawazoe T. Depressive effects of propofol on apoptotic injury and delayed neuronal death after forebrain ischemia in the rat-comparison with nitrous oxide–oxygen–isoflurane. Masui 2000; 49: 130138.
Graham SH, Chen J. Programmed cell death in cerebral ischemia. J Cereb Blood Flow Metab 2001; 21: 99109.
Charriaut-Marlangue C, Remolleau S, Aggoun-Zouaoui D, Ben-Ari Y. Apoptosis and programmed cell death: a role in cerebral ischemia. Biomed Pharmacother 1998; 52: 264269.
Manev H, Kharlamov A, Armstrong DM. Photochemical brain injury in rats triggers DNA fragmentation, p53 and HSP72. Neuroreport 1994; 5: 26612664.
Engelhard K, Werner C, Eberspächer E, et al. The effect of the alpha2-agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats. Anesth Analg 2003; 96: 524531.
Baughman VL, Hoffman WE, Miletich DJ, Albrecht RF, Thomas C. Neurologic outcome in rats following incomplete cerebral ischemia during halothane, isoflurane, or N2O. Anesthesiology 1988; 69: 192198.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed