بررسی بیهوشی‌های مکرر با داروی سئوفلوران در دوران نوجوانی و اثرات آنها بر اختلالات رفتاری و پاتولوژیک در موش‌های صحرایی بالغ‌شده نر و ماده نژاد ویستار

نوع مقاله : مقاله پژوهشی

نویسندگان

1 مرکز تحقیقات الکتروفیزیولوژی، پژوهشکده علوم اعصاب، دانشگاه علوم پزشکی تهران، تهران، ایران

2 مرکز تحقیقات ضایعات مغزی نخاعی، پژوهشکده علوم اعصاب، دانشگاه علوم پزشکی تهران، تهران، ایران

3 گروه بیهوشی، مجتمع بیمارستانی امام خمینی (ره)، دانشگاه علوم پزشکی تهران، تهران، ایران

چکیده

مقدمه و هدف: بیهوشی‌های مکرر در کودکان و نوجوانان در برخی از مداخلات درمانی مانند رادیوتراپی یا سوختگی‌ها ضرورت پیدا می‌کند. تحقیقات نشان داده که بیهوشی عمومی در دوران نوجوانی می‌تواند باعث مرگ سلولی، مشکلات شناختی و بعداً مشکلات عصبی رفتاری در بزرگسالی شود. مطالعه حاضر با هدف ارائه ارزیابی دقیق مورفولوژیکی و عملکردی اثرات طولانی‌مدت مواجهه مکرر با سووفلوران انجام شد.
مواد و روش ها: 28 موش صحرایی نوجوان از روز 24 پس از تولد به‌صورت تصادفی از مادرهای مختلف جدا شده و به چهار گروه نر و ماده کنترل و استنشاقی سئوفلوران (غلظت درصد روزانه به مدت 15 روز) تقسیم شدند. حیوانات بعد از آخرین بیهوشی در روز 38 به مدت 30 تا 35 روز تحت مراقبت و جهت انجام آزمایش‌های رفتاری شامل آزمون‌های ماز آبی موریس، زمینه باز، مربع مرتفع آماده و سپس تغییرات پاتولوژیک با استفاده از رنگ‌آمیزی تولئیدین بلو بررسی و نتایج با از استفاده آزمون‌های آماری t تست غیرزوجی و واریانس‌های یک‌طرفه و دوطرفه آنالیز شد.
نتایج: نتایج مطالعه حاضر نشان داد که در حیوانات نر و ماده، قرارگرفتن مکرر در معرض سووفلوران در دوران نوجوانی می‌تواند باعث اختلال در حافظه فضایی و افزایش اضطراب در بزرگسالی شود. همچنین در حیوانات دریافت‌کننده سووفلوران در مقایسه با گروه کنترل نورون‌های تیره و مرگ سلولی در نواحی هیپوکامپ و کورتکس در حیوانات نر و ماده می‌تواند افزایش یابد.
نتیجه‌گیری: این نتایج ممکن است دیدگاه جدیدی برای درک مکانیسم تکرار قرارگرفتن در معرض اثرات سمی ناشی از سووفلوران در نوجوانی ارائه دهد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Investigating repeated exposure to sevoflurane during adolescence and their effects on behavioral and pathological impairment in adult male and female Wistar rats

نویسندگان [English]

  • Mahdieh Nasiri 1
  • Javad Fahanik Babaei 1
  • Maryam Jafarian 2
  • Seyed Khalil Pestehei 3
1 Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
2 Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
3 Imam Khomeini Hospital Complex, Department of Anesthesiology, Tehran University of Medical Sciences, Tehran, Iran
چکیده [English]

Background and Objective: Repeated anesthesia in adolescence is necessary for some therapeutic interventions, such as radiotherapy or burns. Research has indicated that exposure to general anesthetics during the adolescent period can induce cell death, cognitive and behavioral problems, and later neurobehavioral problems in adulthood. The current study was aimed at providing a detailed morphological and functional evaluation of the long-term impacts of repeated exposure to sevoflurane.
Materials and Methods: In this study, 28 adolescent rats were randomly divided into male and female control groups and inhaled sevoflurane (at a concentration of 2%) daily for 15 days. After last anesthesia, animals of all groups were cared for 30-35 days, and then the effects of repeated exposure to sevoflurane on cognitive functions and anxiety behavior were tested by the Morris water maze, open field, and elevated plus maze. Effects of sevoflurane on cell death and the increase of dark neurons were compared in CA1 of the hippocampus and brain cortex. Data were evaluated using one-way and two-way ANOVA.
Results: Our results indicated that repeated exposures to sevoflurane during adolescence can cause behavioral problems later in adulthood. We found a significant increase in dark neurons and cell death in the sevoflurane group compared to the control group in both male and female animals.
Conclusion: These results may provide a new perspective for understanding the mechanism of repeated exposure to sevoflurane-induced toxic effects in adolescence.

کلیدواژه‌ها [English]

  • Repeated anesthesia
  • Sevoflurane
  • Morris water maze
  • Open field
  • Elevated plus maze
  • Toluidine blue

مراجع

  1. Yang HK. Chungh DS. Hwang JM. The effect of general anesthesia and strabismus surgery on the intellectual abilities of children: a pilot study.American Journal of Ophthalmology 2012;153(4):609-13.
  2. Brambrink AM. Evers AS. Avidan MS. Farber NB. Smith DJ. Zhang X. et al. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 2010;112(4):834-41.
  3. Jevtovic-Todorovic V. Hartman RE. Izumi Y. Benshoff ND. Dikranian K. Zorumski CF. et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. Journal of Neuroscience 2003;23(3):876-82.
  4. Nikizad H. Yon JH. Carter LB. Jevtovic-Todorovic V. Early exposure to general anesthesia causes significant neuronal deletion in the developing rat brain. Annals of the New York Academy of Sciences journal 2007;1122:69-82.
  5. Kanaya A. Emergence agitation in children: risk factors, prevention, and treatment. Journal of Anesthesia   2016;30(2):261-7.
  6. Lerman J. Sikich N. Kleinman S. Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology 1994;80(4):814-24.
  7. Fan CH. Peng B. Zhang FC. The postoperative effect of sevoflurane inhalational anesthesia on cognitive function and inflammatory response of pediatric patients. European Review for Medical and Pharmacological Sciences 2018;22(12):3971-5.
  8. Xu L. Shen J. Yu L. Sun J. McQuillan PM. Hu Z. et al. Role of autophagy in sevoflurane-induced neurotoxicity in neonatal rat hippocampal cells. Brain Research Bulletin 2018;140:291-8.
  9. Patel SS. Goa KL. Sevoflurane. A review of its pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia. Drugs 1996;51(4):658-700.
  10. Makaryus R. Lee H. Feng T. Park JH. Nedergaard M. Jacob Z. et al. Brain maturation in neonatal rodents is impeded by sevoflurane anesthesia. Anesthesiology 2015;123(3):557-68.
  11. Amrock LG. Starner ML. Murphy KL. Baxter MG. Long-term effects of single or multiple neonatal sevoflurane exposures on rat hippocampal ultrastructure. Anesthesiology 2015;122(1):87-95.
  12. Chen C. Shen FY. Zhao X. Zhou T. Xu DJ. Wang ZR. et al. Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats. American Society for Neurochemistry 2015;7(2).
  13. Wang SQ. Fang F. Xue ZG. Cang J. Zhang XG. Neonatal sevoflurane anesthesia induces long-term memory impairment and decreases hippocampal PSD-95 expression without neuronal loss. European Review for Medical and Pharmacological Sciences 2013;17(7):941-50.
  14. Satomoto M. SatohY. Terui K. Miyao H. Takishima K. Ito M. Imaki J. Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice. The American Society of Anesthesiologists, Anesthesiology 2009; (110):628-37.
  15. Fahanik babaei J. Jafarian M. Adeli S. Barzegar behrooz A. Pestehei SK. Cognitive Impairments Induced by Repeated Sevoflurane Exposure During Pre-adolescence in Adult Male and Female Rats: Involvement of Biochemical, Histological and Neuroplasticity Approaches. Journal of Cellular & Molecular Anesthesia  2023;8(4):231-45.
  16. Spear L. Modeling adolescent development and alcohol use in animals. Alcohol Res Health 2000;24(2):115-23.
  17. Spear LP. Adolescent brain development and animal models. Annals of the New York Academy of Sciences journal 2004;1021:23-6.
  18. Spear LP. Brake SC. Periadolescence: age-dependent behavior and psychopharmacological responsivity in rats. Developmental Psychobiology 1983;16(2):83-109
  19. Shen X. Liu Y. Xu S, Zhao Q. Guo X. Shen R. et al. Early life exposure to sevoflurane impairs adulthood spatial memory in the rat. Neurotoxicology 2013;39:45-56.
  20. Kaya Z. Sogut E. Cayli S. Suren M. Arici S. Karaman S. et al. Evaluation of effects of repeated sevoflurane exposure on rat testicular tissue and reproductive hormones. Inhalation Toxicology 2013;25(4):192-8.
  21. Dong Y. Zhang G. Zhang B. Moir RD. Xia W. Marcantonio ER. et al. The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levels. Archives of neurology 2009;66(5):620-31.
  22. Tagawa T. Sakuraba S. Kimura K. Mizoguchi A. Sevoflurane in combination with propofol, not thiopental, induces a more robust neuroapoptosis than sevoflurane alone in the neonatal mouse brain. Journal of Anesthesia 2014;28(6):815-20.
  23. Liu F. Rainosek SW. Frisch-Daiello JL. Patterson TA. Paule MG. Slikker W Jr. et al. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage. Toxicological Sciences 2015;147(2):562-72.
  24. Jimenez-Tellez N. Pehar M. Visser F. Casas-Ortiz A. Rice T. Syed NI. Sevoflurane Exposure in Neonates Perturbs the Expression Patterns of Specific Genes That May Underly the Observed Learning and Memory Deficits. International Journal of Molecular Sciences 2023;24(10).
  25. Wang Y. Li H. Zhao Y. Qin F. Wang L. Jiang L. et al. Neonatal exposure to sevoflurane induces adolescent neurobehavioral dysfunction by interfering with hippocampal glycerophoslipid metabolism in rats. Cerebral Cortex 2023;33(5):1955-71.
  26. Li Y. Liu L. Tian Y. Zhang J. Rapamycin improves sevoflurane induced cognitive dysfunction in aged rats by mediating autophagy through the TLR4/MyD88/NF kappaB signaling pathway. Molecular Medicine Reports 2019;20(4):3085-94.
  27. Zheng H. Dong Y. Xu Z. Crosby G. Culley DJ, Zhang Y, et al. Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspring mice. Anesthesiology 2013;118(3):516-26.
  28. Liang X. Zhang Y. Zhang C. Tang C. Wang Y. Ren J. et al. Effect of repeated neonatal sevoflurane exposure on the learning, memory and synaptic plasticity at juvenile and adult age. American Journal of Translational Research 2017;9(11):4974-83.
  29. Shen Q. Jiang Y. Jia X. Zhou X. Zhou QH. Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice. Iranian Journal of Pharmaceutical Research 2022;21(1):e133971.
  30. Tong D. Ma Z. Su P. Wang S. Xu Y. Zhang LM. et al. Sevoflurane-Induced Neuroapoptosis in Rat Dentate Gyrus Is Activated by Autophagy Through NF-kappaB Signaling on the Late-Stage Progenitor Granule Cells. Frontiers in Cellular Neuroscience 2013;8(2):e57870.
  31. Chen G. Gong M. Yan M. Zhang X. Sevoflurane induces endoplasmic reticulum stress mediated apoptosis in hippocampal neurons of aging rats. PLoS One 2013;8(2):e57870.
  32. Yang Z. Tong Y. Brant JO. Li N. Ju LS. Morey TE. et al. Dexmedetomidine Diminishes, but Does Not Prevent, Developmental Effects of Sevoflurane in Neonatal Rats. Anesthesia & Analgesia 2022;135(4):877-87.
  33. Hu X, Hu X, Huang G. LncRNA MALAT1 is involved in sevoflurane-induced neurotoxicity in developing rats. J Cell Biochem. 2019;120:18209–18.
  34. Yu Z, Wang J, Wang H, Wang J, Cui J, Junzhang P. Effects of sevoflurane exposure during late pregnancy on brain development and beneficial effects of enriched environment on offspring cognition. Cell Mol Neurobiol. 2020b;40:1339–52.
دانشور پزشکی
دوره 31، شماره 6 - شماره پیاپی 169
بهمن و اسفند 1402
صفحه 60-74

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