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Published in: Child's Nervous System 7/2012

01-07-2012 | Original Paper

Neuroprotective effects of propofol, thiopental, etomidate, and midazolam in fetal rat brain in ischemia-reperfusion model

Authors: Ferhat Harman, Askin Esen Hasturk, Mehmet Yaman, Turkan Arca, Kamer Kilinc, Mustafa Fevzi Sargon, Erkan Kaptanoglu

Published in: Child's Nervous System | Issue 7/2012

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Abstract

Purpose

The aim of this study was to investigate the neuroprotective effects of propofol, thiopental, etomidate, and midazolam as anesthetic drugs in fetal rat brain in the ischemia-reperfusion (IR) model.

Methods

Pregnant rats of day 19 were randomly allocated into eight groups. Fetal brain ischemia was induced by clamping the utero-ovarian artery bilaterally for 30 min and reperfusion was achieved by removing the clamps for 60 min. In the control group, fetal rat brains were obtained immediately after laparotomy. In the sham group, fetal rat brains were obtained 90 min after laparotomy. In the IR group, IR procedure was performed. No treatment was given in the IR group. One milliliter intralipid solution, 40 mg/kg propofol, 3 mg/kg thiopental, 0.1 mg/kg etomidate, and 3 mg/kg midazolam was administered intraperitoneally in the vehicle group, propofol group, thiopental group, etomidate group, and midazolam group, respectively, 20 min before IR procedure. At the end of the reperfusion period, the whole brains of the fetal rats were removed for evaluation of thiobarbituric acid reactive substances and for examination by electron microscopy.

Results

According to lipid peroxidation data, all the anesthetic drugs provide neuroprotection; however, ultrastructural findings and mitochondrial scoring confirms that only propofol and midazolam provides a strong neuroprotective effect.

Conclusions

Propofol and midazolam may be used to protect fetal brain in case of acute fetal distress and hypoxic injury as a first choice anesthetic drug in cesarean delivery.
Literature
1.
go back to reference Berger R, Garnier Y, Jensen A (2002) Perinatal brain damage: underlying mechanisms and neuroprotective strategies. J Soc Gynecol Investig 9:319–328PubMedCrossRef Berger R, Garnier Y, Jensen A (2002) Perinatal brain damage: underlying mechanisms and neuroprotective strategies. J Soc Gynecol Investig 9:319–328PubMedCrossRef
2.
go back to reference Jensen A, Garnier Y, Middelanis J, Berger R (2003) Perinatal brain damage-from pathophysiology to prevention. Eur J Obstet Gynecol Reprod Biol 22:S70–S79CrossRef Jensen A, Garnier Y, Middelanis J, Berger R (2003) Perinatal brain damage-from pathophysiology to prevention. Eur J Obstet Gynecol Reprod Biol 22:S70–S79CrossRef
3.
4.
go back to reference Nakai A, Taniuchi Y, Asakura H, Oya A, Yokota A, Koshino T, Araki T (2001) Developmental changes in tolerance to transient intrauterine ischemia in rat cerebral mitochondria. Am J Obstet Gynecol 184:731–735PubMedCrossRef Nakai A, Taniuchi Y, Asakura H, Oya A, Yokota A, Koshino T, Araki T (2001) Developmental changes in tolerance to transient intrauterine ischemia in rat cerebral mitochondria. Am J Obstet Gynecol 184:731–735PubMedCrossRef
5.
go back to reference McCann ME, Bellinger DC, Davidson AJ, Soriano SG (2009) Clinical research approaches to studying pediatric anesthetic neurotoxicity. Neurotoxicology 30:766–771PubMedCrossRef McCann ME, Bellinger DC, Davidson AJ, Soriano SG (2009) Clinical research approaches to studying pediatric anesthetic neurotoxicity. Neurotoxicology 30:766–771PubMedCrossRef
6.
go back to reference Wang C, Slikker W Jr (2008) Strategies and experimental models for evaluating anesthetics: effects on the developing nervous system. Anesth Analg 106:1643–1658PubMedCrossRef Wang C, Slikker W Jr (2008) Strategies and experimental models for evaluating anesthetics: effects on the developing nervous system. Anesth Analg 106:1643–1658PubMedCrossRef
7.
go back to reference Mihara M, Uchiyama M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278PubMedCrossRef Mihara M, Uchiyama M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278PubMedCrossRef
8.
go back to reference Kaptanoglu E, Palaoglu S, Surucu HS, Hayran M, Beskonakli E (2002) Ultrastructural scoring of graded acute spinal cord injury in the rat. J Neurosurg 97:S49–S56 Kaptanoglu E, Palaoglu S, Surucu HS, Hayran M, Beskonakli E (2002) Ultrastructural scoring of graded acute spinal cord injury in the rat. J Neurosurg 97:S49–S56
9.
go back to reference Kaptanoglu E, Sen S, Beskonakli E, Surucu HS, Tuncel M, Kilinc K, Taskin Y (2002) Antioxidant actions and early ultrastructural findings of thiopental and propofol in experimental spinal cord injury. J Neurosurg Anesthesiol 14:114–122PubMedCrossRef Kaptanoglu E, Sen S, Beskonakli E, Surucu HS, Tuncel M, Kilinc K, Taskin Y (2002) Antioxidant actions and early ultrastructural findings of thiopental and propofol in experimental spinal cord injury. J Neurosurg Anesthesiol 14:114–122PubMedCrossRef
10.
go back to reference Ishimoto H, Natori M, Tanaka M, Miyazaki T, Kobayashi T, Yoshimura Y (1997) Role of oxygen-derived free radicals in fetal growth retardation induced by ischemia-reperfusion in rats. Am J Physiol 272:701–705 Ishimoto H, Natori M, Tanaka M, Miyazaki T, Kobayashi T, Yoshimura Y (1997) Role of oxygen-derived free radicals in fetal growth retardation induced by ischemia-reperfusion in rats. Am J Physiol 272:701–705
11.
go back to reference Grow J, Barks JD (2002) Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current concepts. Clin Perinatol 29:585–602PubMedCrossRef Grow J, Barks JD (2002) Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current concepts. Clin Perinatol 29:585–602PubMedCrossRef
12.
go back to reference Solaroglu I, Solaroglu A, Kaptanoglu E, Dede S, Haberal A, Beskonakli E, Kilinc K (2003) Erythropoietin prevents ischemia-reperfusion from inducing oxidative damage in fetal rat brain. Child's Nerv Syst 19:19–22 Solaroglu I, Solaroglu A, Kaptanoglu E, Dede S, Haberal A, Beskonakli E, Kilinc K (2003) Erythropoietin prevents ischemia-reperfusion from inducing oxidative damage in fetal rat brain. Child's Nerv Syst 19:19–22
13.
go back to reference Wakatsuki A, Okatani Y, Shinohara K, Ikenoue N, Fukaya T (2001) Melatonin protects against ischemia-reperfusion-induced oxidative damage to mitochondria in fetal rat brain. J Pineal Res 31:167–172PubMedCrossRef Wakatsuki A, Okatani Y, Shinohara K, Ikenoue N, Fukaya T (2001) Melatonin protects against ischemia-reperfusion-induced oxidative damage to mitochondria in fetal rat brain. J Pineal Res 31:167–172PubMedCrossRef
14.
go back to reference Halliwell B, Gutteridge JM (1985) Oxygen radicals and nervous system. Trends Neurosci 8:22–26CrossRef Halliwell B, Gutteridge JM (1985) Oxygen radicals and nervous system. Trends Neurosci 8:22–26CrossRef
15.
go back to reference Siegel GJ, Agranoff BW, Albers RW, Fischer SK, Uhler MD (1985) Basic neurochemistry: molecular, cellular and medical aspects. Lippincott Raven, Philadelphia Siegel GJ, Agranoff BW, Albers RW, Fischer SK, Uhler MD (1985) Basic neurochemistry: molecular, cellular and medical aspects. Lippincott Raven, Philadelphia
16.
go back to reference Kristian T, Gido G, Kuroda S, Schutz A, Siesjö BK (1998) Calcium metabolism of focal and penumbral tissue in the rats subjected to transient middle cerebral artery occlusion. Exp Brain Res 120:503–509PubMedCrossRef Kristian T, Gido G, Kuroda S, Schutz A, Siesjö BK (1998) Calcium metabolism of focal and penumbral tissue in the rats subjected to transient middle cerebral artery occlusion. Exp Brain Res 120:503–509PubMedCrossRef
17.
go back to reference Takeuchi Y, Morii H, Tamura M, Hayaishi O, Watanabe Y (1991) A possible mechanism of mitochondrial dysfunction during cerebral ischemia: inhibition of mitochondrial respiration activity by arachidonic acid. Arch Biochem Biophys 289:33–38PubMedCrossRef Takeuchi Y, Morii H, Tamura M, Hayaishi O, Watanabe Y (1991) A possible mechanism of mitochondrial dysfunction during cerebral ischemia: inhibition of mitochondrial respiration activity by arachidonic acid. Arch Biochem Biophys 289:33–38PubMedCrossRef
18.
go back to reference Bansal N, Parle M (2010) Soybean supplementation helps reverse age- and scopolamine-induced memory deficits in mice. J Med Food 13:1293–1300PubMedCrossRef Bansal N, Parle M (2010) Soybean supplementation helps reverse age- and scopolamine-induced memory deficits in mice. J Med Food 13:1293–1300PubMedCrossRef
19.
go back to reference Green TR, Bennett SR, Nelson VM (1994) Specificity and properties of propofol as an antioxidant free radical scavenger. Toxicol Appl Pharmacol 129:163–169PubMedCrossRef Green TR, Bennett SR, Nelson VM (1994) Specificity and properties of propofol as an antioxidant free radical scavenger. Toxicol Appl Pharmacol 129:163–169PubMedCrossRef
20.
go back to reference Ito H, Watanabe Y, Isshiki A, Uchino H (1999) Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABAA receptors. Acta Anaesthesiol Scand 43:153–162PubMedCrossRef Ito H, Watanabe Y, Isshiki A, Uchino H (1999) Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABAA receptors. Acta Anaesthesiol Scand 43:153–162PubMedCrossRef
21.
go back to reference Young Y, Menon DK, Tisavipat N, Matta BF, Jones JG (1997) Propofol neuroprotection in a rat model of ischaemia reperfusion injury. Eur J Anaesthesiol 14:320–326PubMedCrossRef Young Y, Menon DK, Tisavipat N, Matta BF, Jones JG (1997) Propofol neuroprotection in a rat model of ischaemia reperfusion injury. Eur J Anaesthesiol 14:320–326PubMedCrossRef
22.
go back to reference Ergun R, Akdemir G, Sen S, Tasci A, Ergungor F (2002) Neuroprotective effects of propofol following global cerebral ischemia in rats. Neurosurg Rev 25:95–98PubMedCrossRef Ergun R, Akdemir G, Sen S, Tasci A, Ergungor F (2002) Neuroprotective effects of propofol following global cerebral ischemia in rats. Neurosurg Rev 25:95–98PubMedCrossRef
23.
go back to reference Solaroglu I, Okutan O, Solaroglu A, Kaptanoglu E, Beskonakli E, Kilinc K (2004) Maternal treatment with propofol attenuates lipid peroxidation after transient intrauterine ischemia in the neonatal rat brain. Biol Neonate 85:221–224PubMedCrossRef Solaroglu I, Okutan O, Solaroglu A, Kaptanoglu E, Beskonakli E, Kilinc K (2004) Maternal treatment with propofol attenuates lipid peroxidation after transient intrauterine ischemia in the neonatal rat brain. Biol Neonate 85:221–224PubMedCrossRef
24.
go back to reference Almaas R, Saugstad OD, Pleasure D, Rootwelt T (2000) Effect of barbiturates on hydroxyl radicals, lipid peroxidation, and hypoxic cell death in human NT2-N neurons. Anesthesiology 92:764–774PubMedCrossRef Almaas R, Saugstad OD, Pleasure D, Rootwelt T (2000) Effect of barbiturates on hydroxyl radicals, lipid peroxidation, and hypoxic cell death in human NT2-N neurons. Anesthesiology 92:764–774PubMedCrossRef
25.
go back to reference Nishina K, Akamatsu H, Mikawa K, Shiga M, Maekawa N, Obara H, Niwa Y (1998) The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions. Anesth Analg 86:159–165PubMed Nishina K, Akamatsu H, Mikawa K, Shiga M, Maekawa N, Obara H, Niwa Y (1998) The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions. Anesth Analg 86:159–165PubMed
26.
go back to reference Sasaki R, Hirota K, Roth SH, Yamazaki M (2005) Anoxic depolarization of rat hippocampal slices is prevented by thiopental but not by propofol or isoflurane. Br J Anaesth 94:486–491PubMedCrossRef Sasaki R, Hirota K, Roth SH, Yamazaki M (2005) Anoxic depolarization of rat hippocampal slices is prevented by thiopental but not by propofol or isoflurane. Br J Anaesth 94:486–491PubMedCrossRef
27.
go back to reference Guo J, White JA, Batjer HH (1995) The protective effects of thiopental on brain stem ischemia. Neurosurgery 37:490–495PubMedCrossRef Guo J, White JA, Batjer HH (1995) The protective effects of thiopental on brain stem ischemia. Neurosurgery 37:490–495PubMedCrossRef
28.
go back to reference Lesser JB, Koorn R, Vloka JD, Kuroda MM, Thys DM (1999) The interaction of temperature with thiopental and etomidate on extracellular dopamine and glutamate levels in Wistar-Kyoto rats subjected to forebrain ischemia. Acta Anaesthesiol Scand 43:989–998PubMedCrossRef Lesser JB, Koorn R, Vloka JD, Kuroda MM, Thys DM (1999) The interaction of temperature with thiopental and etomidate on extracellular dopamine and glutamate levels in Wistar-Kyoto rats subjected to forebrain ischemia. Acta Anaesthesiol Scand 43:989–998PubMedCrossRef
29.
go back to reference Yu Q, Zhou Q, Huang H, Wang Y, Tian S, Duan D (2010) Protective effect of etomidate on spinal cord ischemia-reperfusion injury induced by aortic occlusion in rabbits. Ann Vasc Surg 24:225–232PubMedCrossRef Yu Q, Zhou Q, Huang H, Wang Y, Tian S, Duan D (2010) Protective effect of etomidate on spinal cord ischemia-reperfusion injury induced by aortic occlusion in rabbits. Ann Vasc Surg 24:225–232PubMedCrossRef
30.
go back to reference Drummond JC, McKay LD, Cole DJ, Patel PM (2005) The role of nitric oxide synthase inhibition in the adverse effects of etomidate in the setting of focal cerebral ischemia in rats. Anesth Analg 100:841–846PubMedCrossRef Drummond JC, McKay LD, Cole DJ, Patel PM (2005) The role of nitric oxide synthase inhibition in the adverse effects of etomidate in the setting of focal cerebral ischemia in rats. Anesth Analg 100:841–846PubMedCrossRef
31.
go back to reference Drummond JC, Cole DJ, Patel PM, Reynolds LW (1995) Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury. Neurosurgery 37:742–748PubMedCrossRef Drummond JC, Cole DJ, Patel PM, Reynolds LW (1995) Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury. Neurosurgery 37:742–748PubMedCrossRef
32.
go back to reference Guo J, White JA, Batjer HH (1995) Limited protective effects of etomidate during brainstem ischemia in dogs. J Neurosurg 82:278–283PubMedCrossRef Guo J, White JA, Batjer HH (1995) Limited protective effects of etomidate during brainstem ischemia in dogs. J Neurosurg 82:278–283PubMedCrossRef
33.
go back to reference Lei B, Popp S, Cottrell JE, Kass IS (2009) Effects of midazolam on brain injury after transient focal cerebral ischemia in rats. J Neurosurg Anesthesiol 21:131–139PubMedCrossRef Lei B, Popp S, Cottrell JE, Kass IS (2009) Effects of midazolam on brain injury after transient focal cerebral ischemia in rats. J Neurosurg Anesthesiol 21:131–139PubMedCrossRef
34.
go back to reference Ravlo O, Carl P, Crawford ME, Bach V, Mikkelsen BO, Nielsen HK (1989) A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia: II. Neonates Anesth Analg 68:234–237 Ravlo O, Carl P, Crawford ME, Bach V, Mikkelsen BO, Nielsen HK (1989) A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia: II. Neonates Anesth Analg 68:234–237
35.
go back to reference Chen L, Gong Q, Xiao C (2003) Effects of propofol, midazolam and thiopental sodium on outcome and amino acids accumulation in focal cerebral ischemia-reperfusion in rats. Chin Med J (Engl) 116:292–296 Chen L, Gong Q, Xiao C (2003) Effects of propofol, midazolam and thiopental sodium on outcome and amino acids accumulation in focal cerebral ischemia-reperfusion in rats. Chin Med J (Engl) 116:292–296
36.
go back to reference Kelicen P, Ismailoglu UB, Erdemli O, Sahin-Erdemli I (1997) The effect of propofol and thiopentone on impairment by reactive oxygen species of endothelium-dependent relaxation in rat aortic rings. Eur J Anaesthesiol 14:310–315PubMedCrossRef Kelicen P, Ismailoglu UB, Erdemli O, Sahin-Erdemli I (1997) The effect of propofol and thiopentone on impairment by reactive oxygen species of endothelium-dependent relaxation in rat aortic rings. Eur J Anaesthesiol 14:310–315PubMedCrossRef
Metadata
Title
Neuroprotective effects of propofol, thiopental, etomidate, and midazolam in fetal rat brain in ischemia-reperfusion model
Authors
Ferhat Harman
Askin Esen Hasturk
Mehmet Yaman
Turkan Arca
Kamer Kilinc
Mustafa Fevzi Sargon
Erkan Kaptanoglu
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Child's Nervous System / Issue 7/2012
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-012-1782-0

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