Effects of repeated sevoflurane and rivastigmine on spatial learning and memory in weanling rats

Yıl 2020, Cilt: 5 Sayı: 1, 1 - 5, 20.03.2020

Güneş Özlem Yıldız , Serdar Demirgan Kerem Erkalp Birsen Arslan Hacer Yeter Ayşin Selcan

https://doi.org/10.25000/acem.622517

Öz

Aim: It has been reported that repeated sevoflurane exposure induces cognitive impairment. On the other hand, there is evidence that rivastigmine can attenuate or antagonize the cognitive dysfunctions caused by anesthetic agents. The aims of this study were to determine the effect of repeated sevoflurane exposure on spatial learning and memory (SLM) in weanling rats and to assess whether rivastigmine provides protection against the neurotoxic effects of sevoflurane at this early developmental stage.
Methods: Thirty-two weanling rats were randomly divided into four equal groups: sevoflurane (S: 2% sevoflurane for 2 hours), sevoflurane + rivastigmine (SR: 2% sevoflurane and 2 mg/kg rivastigmine), rivastigmine (R: 2 mg/kg), and control (C: 100% oxygen for 2 hours). Rats were treated four times over 10 days. Four days after the last treatment, the rats were subjected to a Morris water maze test protocol to examine SLM.
Results: The escape latencies of all groups gradually decreased day by day during the training trials performed to evaluate spatial learning (ρ<0.05). Group R showed more improvement than other groups as the rats in this group learned significantly more slowly on the first and second days of the training trials but reached the same levels as Group S and Group SR on the third and last days (ρ<0.05). In the probe trial to evaluate spatial memory, no significant difference was found among the groups for time spent in the ‘platform’ quadrant (ρ>0.05).
Conclusion: Sevoflurane negatively affects learning in weanling rat pups but has no detrimental effect on spatial memory. On the other hand, it can be claimed that sevoflurane offsets the memory-sparing effects of rivastigmine.

Anahtar Kelimeler

Sevoflurane, rivastigmine, spatial learning and memory, rat

Destekleyen Kurum

Istanbul Bagcilar Education and Research Hospital Experimental Animals Ethical Commission

Proje Numarası

Protocol No: 2014/4

Tekrarlı sevofluran ve rivastigminin yavru sıçanların uzaysal öğrenme ve hafıza üzerindeki etkileri

Öz

Amaç: Literatürde tekrarlı sevofluran uygulamalarının bilişsel işlev bozukluklara neden olduğu bildirilmektedir. Diğer yandan, rivastigminin, anestezik ajanların neden olduğu bilişsel işlev bozukluklarını hafifletebileceğine dair bulgular da literatürde yer almaktadır. Çalışmanın amacı tekrarlı sevofluran uygulamasının yavru sıçanların uzaysal öğrenmesine ve hafızasına etkisini ve rivastigmin'in sevofluranın söz konusu nörotoksik etkilerine karşı koruma sağlayıp sağlamadığını araştırmaktır.
Yöntemler: Otuz iki yavru sıçan rastgele olarak dört eşit gruba ayrılmıştır: sevofluran grubu (S: 2 saat boyunca % 2 sevofluran), sevofluran ve rivastigmin grubu (SR: % 2 sevofluran ve 2 mg / kg rivastigmin), rivastigmin grubu (R: 2 mg / kg) ve kontrol grubu (C: 2 saat boyunca % 100 oksijen). Sıçanlara, söz konusu ajanlar 10 gün boyunca dört kez verilmiştir. Son tedaviden dört gün sonra, sıçanlar uzaysal öğrenmeyi ve hafızayı incelenmek üzere Morris Su Labirent Testi protokolüne tabi tutulmuştur.
Bulgular: Uzaysal öğrenmeyi değerlendirmek için yapılan eğitim denemelerinde tüm grupların labirentten kurtulma süreleri günden güne yavaş yavaş azalmıştır (ρ<0.05). Uzaysal hafızayı değerlendirmek için yapılan eğitim testlerinde ise platform kadranında geçirilen süre için gruplar arasında anlamlı bir fark bulunamamıştır (ρ>0.05).
Sonuç: Çalışmada sevofluran, emzirme dönemindeki yavru sıçanların uzaysal öğrenmelerini olumsuz yönde etkilemesine karşın uzaysal hafızaları üzerinde zararlı bir etkisi çıkmamıştır. Diğer yandan sevofluranın, rivastigminin sağladığı hafıza koruyucu etkileri dengelediği gözlemlenmiştir.

Anahtar Kelimeler

Sevofluran, rivastigmin, uzaysal öğrenme ve hafıza, sıçan

Proje Numarası

Protocol No: 2014/4

Kaynakça

• 1. Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelson C, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009;110:796-804.
• 2. DiMaggio C, Sun LS, Li G. Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort. Anesth Analg. 2011;113:1143-51.
• 3. Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, et al. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics. 2011;128:e1053-61.
• 4. Inomata S, Watanabe S, Taguchi M, Okada M. End-tidal sevoflurane concentration for tracheal intubation and minimum alveolar concentration in pediatric patients. Anesthesiology. 1994;80:93-6.
• 5. Murphy KL, Baxter MG. Long-term effects of neonatal single or multiple isoflurane exposures on spatial memory in rats. Front Neurol. 2013;4:87.
• 6. Shen X, Dong Y, Xu Z, Wang H, Miao C, Soriano SG, et al. Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiology. 2013;118:502-15.
• 7. Wang Y, Cheng Y, Liu G, Tian X, Tu X, Wang J. Chronic exposure of gestation rat to sevoflurane impairs offspring brain development. Neurol Sci. 2012;33:535-44.
• 8. Schoen J, Husemann L, Tiemeyer C, Lueloh A, Sedemund-Adib B, Berger K-U, et al. Cognitive function after sevoflurane- vs propofol-based anaesthesia for on-pump cardiac surgery: a randomized controlled trial. Br J Anaesth. 2011;106:840-50.
• 9. Le Freche H, Brouillette J, Fernandez-Gomez F-J, Patin P, Caillierez R, Zommer N, et al. Tau phosphorylation and sevoflurane anesthesia: an association to postoperative cognitive impairment. Anesthesiology. 2012;116:779-87.
• 10. Yin J, Wang S-L, Liu X-B. The effects of general anaesthesia on memory in children: a comparison between propofol and sevoflurane. Anaesthesia. 2014;69:118-23.
• 11. Haseneder R, Starker L, Berkmann J, Kellermann K, Jungwirth B, Blobner M, et al. Sevoflurane anesthesia improves cognitive performance in mice, but does not influence in vitro long-term potentation in hippocampus CA1 stratum radiatum. PLoS One. 2013 May 28 (cited 2019 June 15): 8 (5). Available from: URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064732.
• 12. Culley DJ, Yukhananov RY, Xie Z, Gali RR, Tanzi RE, Crosby G. Altered hippocampal gene expression 2 days after general anesthesia in rats. Eur J Pharmacol. 2006;549:71-8.
• 13. Ma J, Shen B, Stewart LS, Herrick IA, Leung LS. The septohippocampal system participates in general anesthesia. J Neurosci. 2002;22:RC200.
• 14. Fodale V, Santamaria LB. Drugs of anesthesia, central nicotinic receptors and post-operative cognitive dysfunction. Acta Anaesthesiol Scand. 2003;47:1180.
• 15. Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G. Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: a controlled, open 24-month study of 246 patients. Am J Alzheimers Dis Other Demen. 2004;19:333-9.
• 16. Müller T. Rivastigmine in the treatment of patients with Alzheimer’s disease. Neuropsychiatr Dis Treat. 2007;3:211-8.
• 17. Mohan M, Bennett C, Carpenter PK. Rivastigmine for dementia in people with Down syndrome. Cochrane Database Syst Rev (serial online) 2009 Jan 21 (cited 2019 July 3). Available from: URL: https://www.cochranelibrary.com/cdsr/ doi/10.1002/14651858.CD007658/full.
• 18. Ma J, Shen B, Stewart LS, Herrick IA, Leung LS. The septohippocampal system participates in general anesthesia. J Neurosci. 2002;22:RC200.
• 19. Liang YQ, Tang XC. Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats. Acta Pharmacol Sin. 2006;27:1127-36.
• 20. Amenta F, Tayebati SK, Vitali D, Di Tullio MA. Association with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmission. Mech Ageing Dev. 2006;127:173-9.
• 21. Spencer CM, Noble S. Rivastigmine. A review of its use in Alzheimer’s disease. Drugs Aging. 1998;13:391-411.
• 22. Gawel K, Labuz K, Gibula-Bruzda E, Jenda M, Marszalek-Grabska M, Filarowska J, et al. Cholinesterase inhibitors, donepezil and rivastigmine, attenuate spatial memory and cognitive flexibility impairment induced by acute ethanol in the Barnes maze task in rats. Naunyn Schmiedebergs Arch Pharmacol. 2016;389:1059-71.
• 23. Zugno AI, Julião RF, Budni J, Volpato AM, Fraga DB, Pacheco FD, et al Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia. Metab Brain Dis. 2013;28:501-8.
• 24. Bejar C, Wang RH, Weinstock M. Effect of rivastigmine on scopolamine-induced memory impairment in rats. Eur J Pharmacol. 1999;383:231-40.
• 25. Wang RH, Bejar C, Weinstock M. Gender differences in the effect of rivastigmine on brain cholinesterase activity and cognitive function in rats. Neuropharmacology. 2000;39:497-506.
• 26. Nelson MM, Evans HM. Dietary requirements for lactation in the rat and other laboratory animals. Milk: the mammary gland and its secretion. 1961;2:137-91.