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Investigation of the Protective Effect of Different Anesthetics against Cerebral Ischemia-Reperfusion Injury in Rats

Year 2026, Volume: 10 Issue: 1, 32 - 41, 31.01.2026
https://doi.org/10.30621/jbachs.1654813

Abstract

Project Number

013

References

  • Kim J, Thayabaranathan T, Donnan GA, et al. Global stroke statistics 2019. Int J Stroke. 2020; 15:819–838.
  • Li W, Ye A, Ao L. Protective mechanism and treatment of neurogenesis in cerebral ischemia. Neurochem Res. 2020; 45:2258–2277.
  • Thrift AG, Thayabaranathan T, Howard G. Global stroke statistics. Int J Stroke. 2017; 12(1):13–32.
  • Lopez KE, Bouchier H. Lethal and Non-Lethal Functions of Caspases in the DNA Damage Response. Cells 2022; 11:1887.
  • Park SH, Kim Y, Ra JS, et al. Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair. Nucleic Acids Res 2021; 49:11746–11764.
  • Chen H, Chen S, Zhang H, Wang S, Li Y, Meng X. N-methyl-D-aspartate receptor-mediated spinal cord ischemia-reperfusion injury and its protective mechanism. Folia Neuropathol 2022; 60:308-315.
  • Liao W, Wen Y, Yang S, Duan Y, Liu Z. Research progress and perspectives of N-methyl-D-aspartate receptor in myocardial and cerebral ischemia-reperfusion injury: A review. Med 2023; 20:102-42.
  • Tao Z, Lin R, Zhang R, He P, Lei C, Li Y. Ischemia reperfusion myocardium injuries in type 2 diabetic rats: Effects of ketamine and insulin on LC3-II and mTOR expression. Int J Immunopathol Pharmacol 2023; 37:3946320231196450.
  • Suzuki K, Nosyreva E, Hunt KW. Effects of a ketamine metabolite on synaptic NMDAR function. Nature 2017; 546 (7659) doi:10.1038/nature22084.
  • Zanos P, Moaddel R, Morris PJ. Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacol Rev 2018; 70:621–660.
  • Yang K, Ma Y, Xie C, et al. Dexmedetomidine combined with propofol attenuates myocardial ischemia/reperfusion injury by activating the AMPK signaling pathway. Heliyon 2023; 4:9 doi: 10.1016/j.heliyon.2023.e22054. PMID: 38034796; PMCID: PMC10682120.
  • Huang L, Ding L, Yu S, Huang X and Ren Q. Propofol postconditioning alleviates diabetic myocardial ischemia reperfusion injury the miR 200c 3p/AdipoR2/STAT3 signaling pathway. Mol Med Rep 2022; 25: 137.
  • Dost B, Turunc E, Sarikaya OE. Myocardial protection in cardiac surgery: Exploring the influence of anesthetic agents. Eurasian J Med 2023; 55:138-S141.
  • Tas Tuna A, Kocayigit H, Demir G, et al. Investigation of apoptotic effect of propofol, dexmedetomidine and medetomidine on oocyte cumulus granulosa cells in rats. JARSS 2023; 31:50-54.
  • Shiying S, Jingzhong H, Yi R et al. Neuroprotection Against Hypoxic/Ischemic Injury: δ-Opioid Receptors and BDNF-TrkB Pathway. Cell Phys and Biochem 2018; 47:302–315.
  • Lowry O, Rosebrough NI, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265-75.
  • Fridovich I. Superoxide dismutase. Advances in Enzymology. 1974; 41: 35-97.
  • Beutler E. Red Cell Metabolism. A Manual of Biochemical Methods (2nd Edn.). Grune and Stratton Inc, New York. 1984;pp.70.
  • Ohkawa H, Ohishi N, Tagi K. Assay for lipid peroxides in animal tissues by the thiobarbituric acid reaction. Anal Biochem 1979; 95: 351- 8.
  • Noel AA, Hobson RW, Duran WN. Platelet- Activating Factor and Nitric Oxide mediate microvasculer permeability in ıschemia_reperfusion ınjury. Microvas Res 1996; 52.
  • Islekel S, Islekel H, Guner G. Alterations in superoxide dismutase, glutathione peroxidase and catalase activities in experimental cerebral ischemia-reperfusion. Res Exp Med 1999; 199: 167-76.
  • Li J, Wang R, Chen H, Yang Y, Yang X, Wang W. Propofol pretreatment inhibits liver damage in mice with hepatic ischemia/reperfusion injury and protects human hepatocyte in hypoxia/reoxygenation. Turk J Gastroenterol 2023; 34:1171-1179.
  • Fan GB, Li Y, Xu GS, et al. Propofol Inhibits Ferroptotic Cell Death Through the Nrf2/Gpx4 Signaling Pathway in the mouse Model of Cerebral Ischemia-Reperfusion Injury. Neurochem Res 2023; 48:956-966.
  • Hausburg MA, Banton KL, Roman PE. Effects of propofol on ischemia-reperfusion and traumatic brain injury. J of Crit Care.2022; 56:281-287.
  • Farhangi D, Movassaghi S, Nazarnejad MM, & Nadia SZ. Propofol Pretreatment Protects Hippocampal CA1 Neurons from Ischemia-reperfusion Injury in Rat. J of Otorh and Fac Plas Surg 2023; 9: 1–9.
  • Chen Y, Li Z. Protective Effects of Propofol on Rats with Cerebral Ischemia–Reperfusion Injury Via the PI3K/Akt Pathway. J Mol Neurosci 2021; 71: 810–820.
  • Zhongwei X, Lijia C, Youge Q et al. Neuronal brain injury after cerebral ischemic stroke is ameliorated after subsequent administration of (R)-ketamine, but not (S)-ketamine. Pharmaco Biochem and Behav 2020; 191:184-201.
  • Gerb SA, Cook JE, Gochenauer AE. Ketamine tolerance in Sprague-Dawley rats after chronic administration of ketamine, morphine, or cocaine. Comparative medicine 2019; 69: 29–34.
  • Singh I, Gulati S, Orak JK, Singh AK. Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury. Mol and Cel Biochem 1993; 125:97–104.
  • Weiss M. Relationship Between Dissolution Rate in Vitro and Absorption Rate in Vivo of Ketamine Prolonged-Release Tablets. Eur J Drug Metab Pharmacokinet 2023; 48:133–140.
  • Wang HH, Zhou HY, Chen CC, Zhang XL, Cheng G. Propofol attenuation of renal ischemia/reperfusion injury involves heme oxygenase-1. Acta Pharmacol Sin 2007; 28:1175-1180.
  • Ban M, Tonai T, Kohno T. A flavonoid inhibitor of 5-lipoxygenase inhibits leukotriene production following ischemia in gerbil brain. Stroke 1989; 20:248-52.
  • Liang C, Cang J, Wang H, Xue Z. Propofol attenuates cerebral ischemia/reperfusion injury partially using heme oxygenase-1. J Neurosurg Anesthesiol 2013; 25:311-316.
  • Jang JH, Choe EJ, Jung SY, Ko J, Kim DW, Lee JH. A study on the prevalence and prognosis of progressive pulmonary fibrosis: A retrospective observational study. Medicine 2024; 103(20):e38226.
  • Yagmurdur H, Ayyildiz A, Karaguzel E, Akgul T, Ustun H, Germiyanoglu C. Propofol reduces nitric oxide‐induced apoptosis in testicular ischemia–reperfusion injury by downregulating the expression of inducible nitric oxide synthase. Acta Anaesthesiol Scand 2008; 52:350-7.
  • Basu S, Meisert I, Eggensperger E. Time course and attenuation of ischaemia-reperfusion induced oxidative injury by propofol in human renal transplantation. Redox Rep 2007; 12:195 -202.
  • Guzel A, Er U, Tatli M, Aluçlu U, Özkan Ü, Düzenli Y. Serum neuron-specific enolase as a predictor of short–term outcome and its correlation with Glasgow Coma Scala in traumatic brain injury. Neurosurg Rev 2008; 31: 439-445.
  • Murty Ven MR, Viallard JL, Dastugue B. Rapid electrophoretic determination of NSE isoenzymes. Clin Chem 1986; 32:593-596.
  • Cunningham RT, Young IS, Winder J. Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction. Eur J Clin Invest 1991; 21: 497-500.
  • Steinberg R, Gueniau C, Scarna H, Keller A, Worcel M, Pujol JF. Experimental brain ischemia: Neuron-specific enolase level in cerebrospinal fluid as an index of neuronal damage. J Neurochem 1984; 43: 19-24.
  • Hardemark HG, Ericsson N, Kotwica Z. S-100 and neuron specific enolase in CSF after experimental traumatic or focal ischemic brain damage. J Neurosurg1989; 71: 727-731.
  • Hatfield RH, Mckernan RM. CSF neuron specific enolase as a quantitative marker of neuronal damage in rat stroke model. Brain Res 1992; 577: 249-252.

Investigation of the Protective Effect of Different Anesthetics against Cerebral Ischemia-Reperfusion Injury in Rats

Year 2026, Volume: 10 Issue: 1, 32 - 41, 31.01.2026
https://doi.org/10.30621/jbachs.1654813

Abstract

Purpose: Cerebral ischemia/reperfusion (I/R) injury is a serious threat to human health. This study aimed to determine the effects of commonly used intravenous anesthetics in I/R injury on oxidant and antioxidant status and neuron-specific enolase.

Material and Methods: The groups were sham, control, ketamine, thiopental, and propofol. No ischemia-reperfusion was performed in the rats of the control group. At the end of the reperfusion phase, tissue samples were collected for biochemical and histopathologic examinations. We measured biomarkers of oxidative stress. These included catalase, superoxide dismutase, and malondialdehyde using spectrophotometry. The level of neuron-specific enolase was measured by ELISA. Histopathological analysis of the tissue was performed under a light microscope.

Results: In the control group, ischemia-reperfusion significantly increased the malondialdehyde and neuron-specific enolase levels and decreased the level of antioxidant enzymes (p<0.05). However, the ketamine, thiopental, and propofol groups had significantly lower levels of antioxidant enzymes compared to the control group, similar to the sham group (p<0.05). Histopathologic examination of the damage observed in the ketamine, thiopental, and propofol control groups was associated with signs of regeneration.

Conclusion: This study provides in vivo evidence that some anesthetic agents protect against cerebral ischemia-reperfusion injury.

Ethical Statement

KSU MEDİCAL FACULTY

Supporting Institution

YÜKSEK LİSANS PROJESİ

Project Number

013

References

  • Kim J, Thayabaranathan T, Donnan GA, et al. Global stroke statistics 2019. Int J Stroke. 2020; 15:819–838.
  • Li W, Ye A, Ao L. Protective mechanism and treatment of neurogenesis in cerebral ischemia. Neurochem Res. 2020; 45:2258–2277.
  • Thrift AG, Thayabaranathan T, Howard G. Global stroke statistics. Int J Stroke. 2017; 12(1):13–32.
  • Lopez KE, Bouchier H. Lethal and Non-Lethal Functions of Caspases in the DNA Damage Response. Cells 2022; 11:1887.
  • Park SH, Kim Y, Ra JS, et al. Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair. Nucleic Acids Res 2021; 49:11746–11764.
  • Chen H, Chen S, Zhang H, Wang S, Li Y, Meng X. N-methyl-D-aspartate receptor-mediated spinal cord ischemia-reperfusion injury and its protective mechanism. Folia Neuropathol 2022; 60:308-315.
  • Liao W, Wen Y, Yang S, Duan Y, Liu Z. Research progress and perspectives of N-methyl-D-aspartate receptor in myocardial and cerebral ischemia-reperfusion injury: A review. Med 2023; 20:102-42.
  • Tao Z, Lin R, Zhang R, He P, Lei C, Li Y. Ischemia reperfusion myocardium injuries in type 2 diabetic rats: Effects of ketamine and insulin on LC3-II and mTOR expression. Int J Immunopathol Pharmacol 2023; 37:3946320231196450.
  • Suzuki K, Nosyreva E, Hunt KW. Effects of a ketamine metabolite on synaptic NMDAR function. Nature 2017; 546 (7659) doi:10.1038/nature22084.
  • Zanos P, Moaddel R, Morris PJ. Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacol Rev 2018; 70:621–660.
  • Yang K, Ma Y, Xie C, et al. Dexmedetomidine combined with propofol attenuates myocardial ischemia/reperfusion injury by activating the AMPK signaling pathway. Heliyon 2023; 4:9 doi: 10.1016/j.heliyon.2023.e22054. PMID: 38034796; PMCID: PMC10682120.
  • Huang L, Ding L, Yu S, Huang X and Ren Q. Propofol postconditioning alleviates diabetic myocardial ischemia reperfusion injury the miR 200c 3p/AdipoR2/STAT3 signaling pathway. Mol Med Rep 2022; 25: 137.
  • Dost B, Turunc E, Sarikaya OE. Myocardial protection in cardiac surgery: Exploring the influence of anesthetic agents. Eurasian J Med 2023; 55:138-S141.
  • Tas Tuna A, Kocayigit H, Demir G, et al. Investigation of apoptotic effect of propofol, dexmedetomidine and medetomidine on oocyte cumulus granulosa cells in rats. JARSS 2023; 31:50-54.
  • Shiying S, Jingzhong H, Yi R et al. Neuroprotection Against Hypoxic/Ischemic Injury: δ-Opioid Receptors and BDNF-TrkB Pathway. Cell Phys and Biochem 2018; 47:302–315.
  • Lowry O, Rosebrough NI, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265-75.
  • Fridovich I. Superoxide dismutase. Advances in Enzymology. 1974; 41: 35-97.
  • Beutler E. Red Cell Metabolism. A Manual of Biochemical Methods (2nd Edn.). Grune and Stratton Inc, New York. 1984;pp.70.
  • Ohkawa H, Ohishi N, Tagi K. Assay for lipid peroxides in animal tissues by the thiobarbituric acid reaction. Anal Biochem 1979; 95: 351- 8.
  • Noel AA, Hobson RW, Duran WN. Platelet- Activating Factor and Nitric Oxide mediate microvasculer permeability in ıschemia_reperfusion ınjury. Microvas Res 1996; 52.
  • Islekel S, Islekel H, Guner G. Alterations in superoxide dismutase, glutathione peroxidase and catalase activities in experimental cerebral ischemia-reperfusion. Res Exp Med 1999; 199: 167-76.
  • Li J, Wang R, Chen H, Yang Y, Yang X, Wang W. Propofol pretreatment inhibits liver damage in mice with hepatic ischemia/reperfusion injury and protects human hepatocyte in hypoxia/reoxygenation. Turk J Gastroenterol 2023; 34:1171-1179.
  • Fan GB, Li Y, Xu GS, et al. Propofol Inhibits Ferroptotic Cell Death Through the Nrf2/Gpx4 Signaling Pathway in the mouse Model of Cerebral Ischemia-Reperfusion Injury. Neurochem Res 2023; 48:956-966.
  • Hausburg MA, Banton KL, Roman PE. Effects of propofol on ischemia-reperfusion and traumatic brain injury. J of Crit Care.2022; 56:281-287.
  • Farhangi D, Movassaghi S, Nazarnejad MM, & Nadia SZ. Propofol Pretreatment Protects Hippocampal CA1 Neurons from Ischemia-reperfusion Injury in Rat. J of Otorh and Fac Plas Surg 2023; 9: 1–9.
  • Chen Y, Li Z. Protective Effects of Propofol on Rats with Cerebral Ischemia–Reperfusion Injury Via the PI3K/Akt Pathway. J Mol Neurosci 2021; 71: 810–820.
  • Zhongwei X, Lijia C, Youge Q et al. Neuronal brain injury after cerebral ischemic stroke is ameliorated after subsequent administration of (R)-ketamine, but not (S)-ketamine. Pharmaco Biochem and Behav 2020; 191:184-201.
  • Gerb SA, Cook JE, Gochenauer AE. Ketamine tolerance in Sprague-Dawley rats after chronic administration of ketamine, morphine, or cocaine. Comparative medicine 2019; 69: 29–34.
  • Singh I, Gulati S, Orak JK, Singh AK. Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury. Mol and Cel Biochem 1993; 125:97–104.
  • Weiss M. Relationship Between Dissolution Rate in Vitro and Absorption Rate in Vivo of Ketamine Prolonged-Release Tablets. Eur J Drug Metab Pharmacokinet 2023; 48:133–140.
  • Wang HH, Zhou HY, Chen CC, Zhang XL, Cheng G. Propofol attenuation of renal ischemia/reperfusion injury involves heme oxygenase-1. Acta Pharmacol Sin 2007; 28:1175-1180.
  • Ban M, Tonai T, Kohno T. A flavonoid inhibitor of 5-lipoxygenase inhibits leukotriene production following ischemia in gerbil brain. Stroke 1989; 20:248-52.
  • Liang C, Cang J, Wang H, Xue Z. Propofol attenuates cerebral ischemia/reperfusion injury partially using heme oxygenase-1. J Neurosurg Anesthesiol 2013; 25:311-316.
  • Jang JH, Choe EJ, Jung SY, Ko J, Kim DW, Lee JH. A study on the prevalence and prognosis of progressive pulmonary fibrosis: A retrospective observational study. Medicine 2024; 103(20):e38226.
  • Yagmurdur H, Ayyildiz A, Karaguzel E, Akgul T, Ustun H, Germiyanoglu C. Propofol reduces nitric oxide‐induced apoptosis in testicular ischemia–reperfusion injury by downregulating the expression of inducible nitric oxide synthase. Acta Anaesthesiol Scand 2008; 52:350-7.
  • Basu S, Meisert I, Eggensperger E. Time course and attenuation of ischaemia-reperfusion induced oxidative injury by propofol in human renal transplantation. Redox Rep 2007; 12:195 -202.
  • Guzel A, Er U, Tatli M, Aluçlu U, Özkan Ü, Düzenli Y. Serum neuron-specific enolase as a predictor of short–term outcome and its correlation with Glasgow Coma Scala in traumatic brain injury. Neurosurg Rev 2008; 31: 439-445.
  • Murty Ven MR, Viallard JL, Dastugue B. Rapid electrophoretic determination of NSE isoenzymes. Clin Chem 1986; 32:593-596.
  • Cunningham RT, Young IS, Winder J. Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction. Eur J Clin Invest 1991; 21: 497-500.
  • Steinberg R, Gueniau C, Scarna H, Keller A, Worcel M, Pujol JF. Experimental brain ischemia: Neuron-specific enolase level in cerebrospinal fluid as an index of neuronal damage. J Neurochem 1984; 43: 19-24.
  • Hardemark HG, Ericsson N, Kotwica Z. S-100 and neuron specific enolase in CSF after experimental traumatic or focal ischemic brain damage. J Neurosurg1989; 71: 727-731.
  • Hatfield RH, Mckernan RM. CSF neuron specific enolase as a quantitative marker of neuronal damage in rat stroke model. Brain Res 1992; 577: 249-252.
There are 42 citations in total.

Details

Primary Language English
Subjects Anaesthesiology
Journal Section Research Article
Authors

Abdulkadir Aksoy 0009-0002-4114-7327

Ergul Belge Kurutas 0000-0002-6653-4801

İlter Demirhan 0000-0003-0054-7893

Project Number 013
Submission Date March 10, 2025
Acceptance Date December 31, 2025
Publication Date January 31, 2026
Published in Issue Year 2026 Volume: 10 Issue: 1

Cite

APA Aksoy, A., Belge Kurutas, E., & Demirhan, İ. (2026). Investigation of the Protective Effect of Different Anesthetics against Cerebral Ischemia-Reperfusion Injury in Rats. Journal of Basic and Clinical Health Sciences, 10(1), 32-41. https://doi.org/10.30621/jbachs.1654813
AMA Aksoy A, Belge Kurutas E, Demirhan İ. Investigation of the Protective Effect of Different Anesthetics against Cerebral Ischemia-Reperfusion Injury in Rats. JBACHS. January 2026;10(1):32-41. doi:10.30621/jbachs.1654813
Chicago Aksoy, Abdulkadir, Ergul Belge Kurutas, and İlter Demirhan. “Investigation of the Protective Effect of Different Anesthetics Against Cerebral Ischemia-Reperfusion Injury in Rats”. Journal of Basic and Clinical Health Sciences 10, no. 1 (January 2026): 32-41. https://doi.org/10.30621/jbachs.1654813.
EndNote Aksoy A, Belge Kurutas E, Demirhan İ (January 1, 2026) Investigation of the Protective Effect of Different Anesthetics against Cerebral Ischemia-Reperfusion Injury in Rats. Journal of Basic and Clinical Health Sciences 10 1 32–41.
IEEE A. Aksoy, E. Belge Kurutas, and İ. Demirhan, “Investigation of the Protective Effect of Different Anesthetics against Cerebral Ischemia-Reperfusion Injury in Rats”, JBACHS, vol. 10, no. 1, pp. 32–41, 2026, doi: 10.30621/jbachs.1654813.
ISNAD Aksoy, Abdulkadir et al. “Investigation of the Protective Effect of Different Anesthetics Against Cerebral Ischemia-Reperfusion Injury in Rats”. Journal of Basic and Clinical Health Sciences 10/1 (January2026), 32-41. https://doi.org/10.30621/jbachs.1654813.
JAMA Aksoy A, Belge Kurutas E, Demirhan İ. Investigation of the Protective Effect of Different Anesthetics against Cerebral Ischemia-Reperfusion Injury in Rats. JBACHS. 2026;10:32–41.
MLA Aksoy, Abdulkadir et al. “Investigation of the Protective Effect of Different Anesthetics Against Cerebral Ischemia-Reperfusion Injury in Rats”. Journal of Basic and Clinical Health Sciences, vol. 10, no. 1, 2026, pp. 32-41, doi:10.30621/jbachs.1654813.
Vancouver Aksoy A, Belge Kurutas E, Demirhan İ. Investigation of the Protective Effect of Different Anesthetics against Cerebral Ischemia-Reperfusion Injury in Rats. JBACHS. 2026;10(1):32-41.