The Effects of Memantine on Recovery from Propofol Anesthesia, Cognitive Function and Pain in Elderly Rats

  • Büşra Sözen
  • Yusuf Ünal
  • Ülkü Sabuncu
  • Hatice Paşaoğlu
  • Mustafa Arslan Gazi Üniversitesi Tıp Fakültesi

Abstract

Objective: Postoperative cognitive dysfunction (POCD) is a frequent complication after anesthesia and propofol is an intravenous anesthetic agent that has been proved to cause cognitive dysfunction. There are many risk factors such as age for POCD. Memantine has beneficial effects on memory deficits and learning process. Besides, it has neuroprotective effects and can be used in treatment of chronic pain syndromes. This study was designed to determine the effects of memantine on recovery, cognitive functions and pain in aged rats undergoing general anesthesia with propofol. Materials and Methods: Thirty aged (>12 months) Wistar rats were divided into 5 groups randomly. For Group C 0,9% NaCl (1 mL i.p.) was administered at 21.day, for Group P propofol (100 mg/kg i.p.) was administered at 21st day, for Group (oral memantine+propofol) OMP propofol (100 mg/kg, i.p.) was administered after 20 days of treatment with 20 mg/kg/day oral memantine, for Group (oral memantine) OM memantine (20 mg/kg/day oral) was administered for 20 days, for Group (intraperitoneal memantine+propofol) IPMP propofol (100 mg/kg) was administered  after 30 minutes memantine (1 mg/kg i.p. in 1 mL 0,9% NaCl)  were applied. Recovery was evaluated by tail pinch test, cognitive functions were evaluated by radial arm maze (RAM), S100 β and neuron-specific enolase (NSE) and pain was evaluated by hot-plate. Results:  In this study recovery times were shorter   in Group OMP and Group IPMP when compared to Group P (p=0,011, p=0,034, respectively). Cognitive functions of rats in Group OMP and Group IPMP were better than Group P for the first value of recovery (p<0,05). Hot-plate test values in all groups, except group C were longer at all time points when compared to control values (p<0,05).  NSE and S100 β levels were higher in Group P when compared to Group C. The levels of S100 β and NSE levels were comparable in Groups C, OMP and IPMP. Conclusion:  This study showed that memantine has beneficial effects on negative effects of propofol on recovery, cognitive functions and pain.

References

Ward B, Imarengiaye C, Peirovy J, Chung F. Cognitive function is minimally impaired after ambulatory surgery. Can J Anesth 2005; 52: 1017–21.

Selwood A, Orrell M. Long term cognitive dysfunction in older people after non-cardiac surgery. BMJ 2004; 328: 120–1.

Robinson TN, Wu DS, Pointer LF, Dunn CL, Moss M. Preoperative cognitive dysfunction is related to adverse postoperative outcomes in the elderly. J Am Coll Surg. 2012; 215: 12-7.

Tüzüner F. Anestezi Yoğun Bakım Ağrı. Nobel Yayınevi 2010; 1087-120.

Morgan GE. Mikhail MS. Morgan and Mikhail's Clinical Anesthesiology, 4th edition. The Mc Graw Hill ed 2008; 951-8.

Miller RD. Miller Anestezi. Çeviri editörü Demet Aydın: Güven Bilimsel. 6. Baskı. 2010; 317-79.

Minkeviciene R, Banerjee P, Tanila H. Memantine Improves Spatial Learning in a Transgenic Mouse Model of Alzheimer’s Disease. J Pharmacol Exp Ther 2004; 311: 677-82.

Onogi H, Ishigaki S, Nakagawasai O, Arai-Kato Y, Arai Y, et al. Influence of Memantine on Brain Monoaminergic Neurotransmission Parameters in Mice: Neurochemical and Behavioral Study. Biol Pharm Bull 2009;32(5):850-5.

Culmsee C, Junker V, Kremers W, Thal S, Plesnila N, Krieglstein J. Combination Therapy in Ischemic Stroke: Synergistic Neuroprotective Effects of Memantine and Clenbuterol. Stroke 2004;35:5; 1197-202.

Kunimatsu T, Misaki T, Hirose N, Tsuboi E, Takahashi I, Ohki H, et al. Postoperative mental disorder following prolonged oral surgery. J Oral Sci 2004; 46: 71–4.

Nishikawa K, Nakayama M, Omote K, Namiki A. Recovery characteristics and post-operative delirium after long-duration laparoscope-assisted surgery in elderly patients; propofol-based vs. sevoflurane-based anesthesia. Acta Anaesthesiol Scand 2004; 48: 162–8.

McShane R, Areosa Sastre A, Minakaran N. Memantine for Dementia. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003154

Wise LE, Lichtman AH. The uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial arm maze memory task. Eur J Pharmacol 2007; 575: 98–102.

Sonkusare SK, Kaul CL, Ramarao P. Dementia of Alzheimer’s disease and other neurodegenerative disorders-memantine, a new hope. Pharmacol Res 2005; 51(1):1-17.

Emik U, Unal Y, Arslan M, Demirel CB. The effects of memantine on recovery, cognitive functions, and pain after propofol anesthesia. Braz J Anesthesiol 2016; 66(5): 485-9.

Brosnan RJ. GABA(A) receptor antagonism increases NMDA receptor inhibition by isoflurane at a minimum alveolar concentration. Vet Anaesth Analg 2011; 38: 231-9.

Kuroda Y, Strebel S, Rafferty C, Bullock R. Neuroprotective doses of N-methyl-D-aspartate receptor antagonists profoundly reduce the minimum alveolar anesthetic concentration (MAC) for isoflurane in rats. Anesth Analg 1993;77: 795-800.

Ali MS, Harmer M, Vaughan R. Serum S100 protein as a marker of cerebral damage during cardiac surgery. Br J Anaesth 2000; 85: 287–98.

Gan GS, Wang YL, Chen LM, Shen QX, Yu JB, Qiu W. Effects of propofol and isoflurane on serum neuron-specific enolase level in surgical patients with acute craniocerebral trauma: a comparative study. Di Yi Jun Yi Da Xue Xue Bao 2005; 25(7):858-60 (abstract).

Linstedt U, Meyer O, Kropp P, Berkau A, Tapp E, Zenz M. Serum Concentration of S-100 protein in Assessment of Cognitive Dysfunction After General Anesthesia in Different Types of Surgery. Acta Anaesthesiol Scand 2002; 46(4):384-9.

Liu Y, Xu Y, Li DZ, Shi Y, Ye M. Comparison of S100B and NSE between cardiac surgery and interventional therapy for children. Pediatr Cardiol 2009; 30(7):893-7.

Schick U, Döhnert J, Meyer JJ, Vitzthum HE. Prognostic significance of SSEP, BAEP and serum S–100β monitoring after aneurysm surgery. Acta Neurol Scand 2003; 108: 161–9.

Böttiger BW, Möbes S, Glätzer R, Bauer H, Gries A, Bärtsch P, et al. Astroglial protein S–100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans. Circulation 2001;103: 2694–8.

Einav S, Shoshan Y, Ovadia H, Matot I, Hersch M, Itshayek E. Early postoperative serum S100 beta levels predict ongoing brain damage after meningioma surgery. Crit Care 2006;10(5):R141.

Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist: review of preclinical data. Neuropharmacology 1999; 38(6):735-67.

Chen SR, Samoriski G, Pan HL. Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain. Neuropharmacology 2009;57(2):121-6.

Published
2020-03-10
Section
Original Research