The Effects of Memantine on Cognitive Function and Pain after Sevoflurane and Desflurane Anesthesia in Streptozotocin Induced Diabetic Rats

  • Ünal Taş
  • Mehmet Akçabay
  • Mustafa Arslan Gazi Üniversitesi Tıp Fakültesi
  • Yusuf Ünal

Abstract

Objective: Postoperative cognitive dysfunction (POCD) refers to a wide range of alterations which effect memory, information processing and executive function after anesthesia and, the mechanism is still not properly defined. Diabetes is a chronic metabolic disease which has a negative impact on cognitive function and leads to impairment of perception of pain by causing peripheral neuropathy. Sevoflurane and desflurane are anesthetic agents which are shown to cause POCD in many studies. Memantine is an agent which has a positive contribution on memory and learning; also known as neuroprotective and used in chronic pain treatment. In this study, we aim to investigate the effects of memantine, after sevoflurane and desflurane anesthesia on cognitive dysfunction and pain levels in diabetic rats. Materials and Methods: In our study, we used 42, old (>12 months) Wistar Albino rats, 6 of them were grouped as control group (Group C). We have injected 55 mg/kg streptozotocin (i.p) in the other wistar rats and measured blood glucose and weight. Diabetic 36 rats were randomized into 6 groups (n=6) and groups were defined as Group DC, Group DM, Group DS, Group DD, Group DSM, Group DDM and control group Group C. During 30 days we added 20 mg/kg memantine into the drinking water of Group DM, Group DSM and Group DDM’s rats. We measured radial arm maze (RAM) and hot plate values of 30 days-followed up rats weekly. At the end of 30 days we gave anesthesia to sevoflurane and desflurane groups in 2 hours-long period and after that we measured 0. 1. and 2. hours RAM and hot plate values of this rats and other rats. Results: In the groups of which only variant was diabetes (until the study day Group C and Group DC, Group DS and Group DD, groups which weren’t given memantine), we compared the results and we conclude that diabetes has negative impact on cognitive function. Similarly, in the groups of which only variant was sevoflurane (Group DS and Group DC) or was desflurane (Group DD and Group DC) we compared the results and we conclude that our inhaler agents effect cognitive functions negatively. And yet, in the groups of which only variant was just inhaler agents (Group DS and Group DD; Group DSM and Group DDM), inhaler agents have similar effects on cognitive function and recovery. And finally, in the rat groups of which only variant was memantine (Group DC and Group DM, Group DSM and Group DS, Group DDM and Group DD), we observe that memantine fasten recovery time and has a positive effects on cognitive functions. In addition to that, we compared the hot plate measurements between 30 days followed-up diabetic rats which were not given memantine (Group DC, Group DS and Group DD) and diabetic rats which were given memantine (Group DM, Group DSM, Group DDM) and between the groups on the study day which had only variant memantine (Group DSM and Group DS; Group DDM and Group DD). The hot plate values show us memantine has an analgesic effect. Conclusion: In conclusion, administration of memantine in diabetic rats has positive effect on recovery, cognitive functions and pain levels after anesthesia with sevoflurane or desflurane.

References

Smith PL, Newman SP, Ell PJ, et al. Cerebral consequence of cardiopulmonary bypass. Lancet 1986; 1: 823-5.

Işık B. Relationship between anesthesia and cognitive functions. Turkiye Klinikleri J Anest Reanim 2004; 2: 94-102.

Davies RG, Myles PS, Graham JM. A comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy-a systematic review and meta-analysis of randomized trials. Br J Anaesth 2006;96: 418-26.

Li ZG, Zhang W, Grunberger G, et al. Hipocampal neuronal apoptosis in type 1 diabetes. Brain Res 2002; 946 (2): 221-31.

Mobius H. Pharmacological Rationale for Memantine in Choronic Cerebral Hypoperfusion, Especially Vascular Demantia. Alzheimer Disease and Associated Disorders 1999; 13: 172-8.

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

Culmsee C, Junker V, Kremers W, et al. Combination Therapy in Ischemic Stroke: Synergistic Neuroprotective Effects of Memantine and Clenbuterol. Stroke 2004; 35: 1197-202.

Berrino L, Oliva P, Massimo F, et al. Antinociceptive effect in mice of intraperitoneal N-methyl-D-aspartat Receptor Antagonists in the Formalin Test. Eur J Pain 2003; 7:131-7.

Sinclair AJ, Allard I, Bayer A. Observations of diabetes care in long term instituonal settings with measures of cognitive function and dependency. Diabetes Care 1997; 20: 778-84.

Dey J, Misra A, Desai NG, et al. Cognitive function in younger type II diabetes. Diabetes Care 1997; 20: 32-35.

Meneilly GS, Hill A. Alterations in glucose metabolism in patients with Alzheimer's disease. J Am Geriatr Soc 1993; 41: 710-4.

Cottrell JE. We care, therefore we are: anesthesia-related morbidity and mortality: the 46th Rovenstine lecture. Anesthesiology 2008; 109: 377-88.

Eckenhoff RG, Johansson JS, Wei H, et al. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 2004;101:703-9.

Hanning CD, Blokland A, Johnson M, et al. Effects of repeated anaesthesia on central cholinergic function in the rat cerebral cortex. Eur J Anaesthesiol 2003; 20: 93-7.

McShane R, Areosa S, Minakaran N. Memantine for Dementia. The Cochrane Library 2009; 1: 1-43.

Wise LE and 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.

Zajaczkowski W, Quack G, Danysz W (1996) Infusion of (+)-MK-801 and memantine-contrasting effects on radial maze learning in rats with entorhinal cortex lesion. Eur J Pharmacol 1996; 296(3):239–6.

Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist: review of preclinical data. Neuropharmacol 1999; 38: 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: 121-6.

Alexander JK, DeVries AC, Kigerl KA, et al. Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation. Brain Behav Immun 2009; 23: 851-60.

Hackworth RJ, Tokarz KA, Fowler IM, et al. Profound pain reduction after induction of memantine treatment in two patients with severe phantom limb pain. Anesth Analg 2008; 107(4): 1377-9.

Grande LA, O'Donnell BR, Fitzgibbon DR, et al. Ultra-low dose ketamine and memantine treatment for pain in an opioid-tolerant oncology patient. Anesth Analg 2008; 107(4): 1380-3.

Viletti G, Bergamaschi M, Bassani F, et al. Antinociceptive Activity of the N-Methyl-D-aspartate Receptor Antagonist N (2-Indanyl)-glycinamide Hydrochloride (CHF3381) in Experimental Models of Inflammatory and Neuropathic Pain. JPET 2003; 306:804–14.

Published
2020-03-10
Section
Original Research