The effects of ketamine on balance behavior and histology changes of cerebellum in short- and long- term anesthesia in rats

Authors
Behrooz Yahyaei
Leyla Khojasteh
Marziyeh Saeedmehr
Department of Medical sciences, Islamic Azad University, Shahrood Branch, Shahrood, Iran
Abstract
Introduction: Because of impotance of anesthesia in surgery and also high usage of ketamine for keeping anesthesia, this study was done for investigating on effects of short- and long- term anesthesia by ketamine in cerebellum in rats.

Materials and Method: Thirty rats were chosen in both sex with weight about 190 g and age about 8-12 weeks divided into 6 groups. Firstly, balance test was done for each of the groups and anesthesia induced for a month. The two control groups (male and female) that they were not anesthetized. Another the two groups (male and female) were anesthetized by ketamine (25 mg/kg) three times in the week (short term anesthesia), and final the other 2 groups were anesthezed by ketamin (75 mg/kg) once a week (long- term anesthesia).

The balance test was done for the whole groups after a month. The rats’s cerebellum were removed and their histological slides were examined

Result: The histological examination showed the mild to moderate changes in some layers of the cerebellum. However, in terms of balance, the studies did not show significant differences among the groups.

Conclusion: Our result showed that ketamine has a mild effect on the cerebellum. There was no significant difference between the short-term anesthetic groups with a dose of 25 mg/kg and the long-term groups with a dose of 75 mg/kg.
Keywords
Ketamine
cerebellum
Histology
balance
rat
Shahri S. The effect of frequent anesthesia with Ketamine on seizure by PTZ in neonate period and response to pain in puberty in rat [dissertation]. Basic sciences school: Ferdowsi University of Mashhad; 2011,73.
Miller RD, Pardo M. Basics of anesthesia. 6th ed. Saunders: 2011.
Bijker JB, van Klei WA, Kappen TH, van Wolfswinkel L, Moons KG, Kalkman CJ. Incidence of intraoperative hypotension as a function of the chosen definition: literature definitions applied to a retrospective cohort using automated data collection. Anesthesiology 2007;107(2):213-20.
Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, et al. Early exposure tocommon anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003;23(3):876-82.
Annetta MG, Iemma D, Garisto C, Tafani C, Proietti R. Ketamin: new indication for an old drug. Curr Drug Targets 2005;6(7):789-94.
Granry JC, Dube L, Turroques H, Conreux F. Ketamine: new uses for an old drug. Curr Opin Anaesthesiol 2000;13(3):299-302.
Ivani G, Vercellino C, Tonnetti F. Ketamin: a new look to an old drug. Minerva Anestesiol 2003;69(5):468-71.
Stanley FM. Sedation. 8 th ed. Philadelphia: Mosby٫ Elsevier 2014 p.50-60.
Clark WC, Chokhavatia SS, Kashani A, Clark SB. Chapter 6 - Pain Measurement. In: Argoff CE, McCleane G, editors. Pain Management Secrets. 3rd ed. Philadelphia: Mosby; 2009. p.42-52.
Ducharme J. Acute pain and pain control: State of the art. Ann Emerg Med 2000;35(6):592-603.
Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, et al. Blockade of NMDA receptors andapoptotic neurodegeneration in the developing brain. Science 1999;283(5398):70-4.
Haberny KA, Paule MG, Scallet AC, Sistare FD, LesterDS, Hanig JP, et al. Ontogeny of the N-methyl-D-aspartate (NMDA) receptor system and susceptibility to neurotoxicity. Toxicol Sci 2002;68(1):9-17.
Duman RS, Li N, Liu RJ, Duric V, Aghajanian G. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology 2012;62(1):35-41.
Wai MS1, Luan P, Jiang Y, Chan WM, Tsui TY, Tang HC, et al. Long term Ketamine and Ketamine plus alcohol toxicity: What can we learn from animal models?. Mini Rev Med Chem 2013;13(2):273-9.
Hayashi H, Dikkes P, Soriano SG. Repeated administration of ketamine may lead to neuronal degeneration in the developing rat brain. Paediatr Anaesth 2002;12(9):770-4.
Greene SA. Chronic pain: phathophysiology and treatment implications. Top Companion Anim Med 2010;25(1):5-9.
Mescher AL. Junqueira′s basic hisyology. 13th ed. 2013.
Hall, John E. Guyton and Hall Textbook of Medical Physiology. 13th edition. Philadelphia, PA: Elsevier, 2016
Gray H. Henry Gray′s Anatomy of the Human Body 2013;3th ed.
Suárez A, Macadar O. The effect of general and spinal anesttesia on balance control in elderly patients. Int Tinnitus J 2008;14(2):146-51.
Moazedy AA, Mojadam S, Parham Gh.A. The effect of oral and central administration of ALCL3 on movement and coordination in adult male rat. Journal of Animal Researches 2014;26(4):460-7.
Karambakhsh A٫ Noori Mogehi SMH٫ Hasanzade GR٫Takzaree N. Excitatoryandinhibitory effects of nitroc oxide on weight٫size٫ and histological changes of rat cerebellum. Tehran Univ Med J 2013;70(10):595-600.
Soleymani asl S, Aghaei O, Shekarriz N, Molavi N, Mehdizade M. Effects of chronic treatment of Ketamin on hippocampus cell count of adult rats. Horizon Med Sci 2013;19(1):35-9.
Ordek G, Groth JD, Sahin M. Differential effects of ketamine/xylazine anesthesia on the cerebral and cerebellar cortical activities in the rat. J Neurophysiol 2013;109(5):1435-43.
Boczek T, Lisek M, Ferenc B, Wiktorska M, Ivchevska I, Zylinska L. Region-specific effects of repeated Ketamine administration on the presynaptic GABAergic neurochemistry in rat brain. Neurochem Int 2015;91:13-25.
Olutoye OA, Sheikh F, Zamora IJ, Yu L, Akinkuotu AC, Adesina AM, et al. Repeated isoflurane and neuroapoptosis in the midgestation fetal sheep brain.Am J Obstet Gynecol 2016;214(4):542.