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The effects of memantine on lipid peroxidation following closed-head trauma in rats

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Abstract

Memantine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Unlike other NMDA antagonists, it has been used clinically for years for the treatment of Parkinson’s disease, spasticity, and dementia without serious side effects. We aimed to investigate the therapeutic efficacy of memantine on a closed head trauma model. A total of 132 adult male Sprague–Dawley rats were randomly divided into four groups: sham-operated, control (closed head trauma), sham-vehicle (closed head trauma + saline), treatment (closed head trauma + memantine, 10 mg/kg, i.p.). A cranial impact was delivered to the skull, just in front of the coronal suture, over the left hemisphere, from the height of 7 cm. Saline or memantine were applied 15 min after trauma. Rats were euthanased 0.5, 1, 2, 6, 24, 48 h after trauma. Brain tissue samples were taken 5 mm away from the left frontal pole and also from the corresponding point of the contralateral hemispheres. Malondialdehyde activity (MDA) was considered to reflect the degree of lipid peroxidation. The MDA levels continued to increase for the first 2 h after the injury, then started to decrease gradually. Memantine treatment significantly reduced lipid peroxidation levels in the treatment group compared with other groups (P<0.01). The findings of the present study indicate that memantine provides beneficial effects after closed head trauma in rats.

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References

  1. Baethmann A, Maier-Hauff K, Schurer L, Large M, Guggenbichler C, Vogt W (1989) Release of glutamate and free fatty acids in vasogenic brain edema. J Neurosurg 70:578–591

    Google Scholar 

  2. Blandpied TA, Boeckman FA, Aizenman E, Johnson JW (1992) Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol 77:309–323

    Google Scholar 

  3. Block F, Schwarz M (1996) Memantine reduces functional and morphological consequences induced by global ischemia in rats. Neurosci Lett 208:41–44

    Article  Google Scholar 

  4. Bormann J (1989) Memantine is a potent blocker of N-methyl-D-aspartate (NMDA) receptor channels. Eur J Pharmacol 166:591–592

    Article  Google Scholar 

  5. Chen HS, Lipton SA (1997) Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism. J Physiol 499:27–46

    CAS  PubMed  Google Scholar 

  6. Chen HV, Pellegrini JW, Aggarwal SK, Lei SZ, Warach S (1992) Open-channel block N-methyl-D-aspartate (NMDA) responses by memantine. Therapeutic advantage agonist NMDA receptor-mediated neurotoxicity. J Neurosci 12:4427–4436

    Google Scholar 

  7. Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634

    CAS  PubMed  Google Scholar 

  8. Cristofori L, Tavazzi B, Gambin R, Vagnozzi R, Vivenza C, Amorini AM (2001) Early onset of lipid peroxidation after human traumatic brain injury: a fatal limitation for the free radical scavenger pharmacological therapy. J Investig Med 49:450–458

    Google Scholar 

  9. Faden AI, Demediuk P, Panter SS, Vink R (1989) The role of excitatory aminoacids and NMDA receptors in traumatic brain injury. Science 244:798–800

    CAS  PubMed  Google Scholar 

  10. Görgülü A, Kırış T, Çobanoğlu S, Ünal F, İzgi N, Yanık B, Küçük M (2000) Reduction of edema and infarction by memantine and MK-801 after focal cerebral ischemia and reperfusion in rat. Acta Neurochir (Wien) 42:1287–1292

    Google Scholar 

  11. Görgülü A, Kırış T, Ünal F, Türkoğlu Ü, Küçük M, Çobanoğlu S (1999) Protective effect of the N-methyl-D-aspartate antagonists MK-801 and CPP on cold-induced brain oedema. Acta Neurochir (Wien) 141:93–98

    Article  Google Scholar 

  12. Hsiang JN, Wang JV, Ip SM, Stadlin A, Yu AL, Poon WS (1997) The time course and regional variations of lipid peroxidation after diffuse brain injury in rats. Acta Neurochir (Wien) 139:464–468

    Google Scholar 

  13. Ikeda Y, Long DM (1990) The molecular basis of brain injury and brain edema: the role of oxygen free radicals. Neurosurgery 27:1–11

    Article  Google Scholar 

  14. Kanthan R, Shuaib A (1995) Clinical evaluation of extracellular amino acids in severe head trauma by intracerebral in vivo microdialysis. J Neurol Neurosurg Psychiatry 59:326–327

    CAS  PubMed  Google Scholar 

  15. Kaplanski J, Asa I, Artru AA, Azez A, Ivashkova Y, Rudich Z, Pruneau D, Shapira Y (2003) LF0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats. Resuscitation 56:207–213

    Article  Google Scholar 

  16. Katayama Y, Becker DP, Tamura T, Hovda DA (1990) Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg 73:889–900

    Google Scholar 

  17. Kemp JA, Foster AC, Wong EHF (1987) Non-competitive antagonists of excitatory amino acid receptors. Trends Neurosci 10:294–298

    Google Scholar 

  18. Koek W, Woods JH, Winger GD (1988) MK-801, a proposed non-competitive antagonists of excitatory amino acid neurotransmission, produces phencylidine-like behavioral effects in pigeons, rats and rhesus monkeys. J Pharmacol Exp Ther 245:969–974

    Google Scholar 

  19. Koura SS, Doppenberg EM, Marmarou A, Choi S, Young HF (1998) Relationship between excitatory amino acid release and outcome after severe human head injury. Acta Neurochir (Wien) 7:244–246

    Google Scholar 

  20. Kuchiwaki H, Inao S, Yamamoto M, Yoshida K, Sugita K (1994) An assessment of progression of brain edema with amino acid levels in cerebrospinal fluid and charges in electroencephalogram in an adult cat model of cold brain injury. Acta Neurochir (Wien) 60:62–64

    Google Scholar 

  21. Lowry OH, Rosenbrought NJ, Farr AL (1951) Protein measurement with the folin phenol reagents. J Biol Chem 193:265–277

    CAS  PubMed  Google Scholar 

  22. Marshall LF (2000) Head injury: recent past, present, and future. Neurosurgery 47:546–561

    Article  Google Scholar 

  23. Nasr MS, Peruche B, Robberg C, Mennel HD, Krieglstein J (1990) Neuroprotective effect of memantine demonstrated in vivo and vitro. Eur J Pharmacol 185:19–24

    Article  Google Scholar 

  24. Marshall LF, Maas AI, Marshall SB, Bricolo A, Fearnside M, Iannotti F, Klauber MR, Lagarrigue J, Lobato R, Persson L, Pickard JD, Piek J, Servadei F, Wellis GN, Morris GF, Means ED, Musch B (1998) A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury. J Neurosurg 89:519–525

    Google Scholar 

  25. McCall JM, Braughler JM, Hall ED (1987) Lipid peroxidation and the role of oxygen radicals in CNS injury. Acta Anaesthesiol Belg 38:373–379

    Google Scholar 

  26. McIntosh TK, Vink R, Soares H, Hayes R, Simon R (1990) Effect of non-competitive blockade of N-methyl-D-aspartate receptor on the neurochemical sequelae of experimental brain injury. J Neurochem 55:1170–1179

    Google Scholar 

  27. Nilsson P, Hillerd L, Ponten U, Ungerstedt U (1990) Charges in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab 10:631–637

    Google Scholar 

  28. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    CAS  PubMed  Google Scholar 

  29. Orgogozo JM, Rigaud AS, Stoffler A, Mobius HJ, Forette F (2002) Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial. Stroke 33:1834–1839

    Article  Google Scholar 

  30. Paolin A, Nardin L, Gaetani P, Rodriguez Y, Baena R, Pansarasa O, Marzatico F (2002) Oxidative damage after severe head injury and its relationship to neurological outcome. Neurosurgery 51:949–954

    Article  Google Scholar 

  31. Pellegrini JW, Lipton SA (1993) Delayed administration of memantine prevents N-methyl-D-aspartate receptor-mediated neurotoxicity. Ann Neurol 33:403–407

    Article  Google Scholar 

  32. Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic–ischemic brain damage. Ann Neurol 19:105–111

    Article  Google Scholar 

  33. Rao VL, Dogan A, Todd KG, Bowen KK, Dempsey RJ (2001) Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. Brain Res 911:96–100

    Article  Google Scholar 

  34. Sang CN, Booher S, Gilron I, Parada S, Max MB (2002) Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia. Anesthesiology 96:1053–1061

    Article  Google Scholar 

  35. Scatton B, Carter C, Benavidas J, Giroux C (1991) N-methyl-D-aspartate receptor antagonists: a novel therapeutic perspective for the treatment of ischemic brain injury. Cerebrovasc Dis 1:121–135

    Google Scholar 

  36. Schmidley JW (1990) Free radicals in central nervous system ischemia. Stroke 21:1086–1090

    Google Scholar 

  37. Shapira Y, Shohami E, Sidi A, Soffer D, Freeman S, Cotev S (1988) Experimental closed head injury in rats: mechanical, pathophysiologic and neurologic properties. Crit Care Med 16:258–265

    Google Scholar 

  38. Shapira Y, Yadid G, Cotev S, Niska A, Shohami E (1990) Protective effect of MK-801 in experimental brain injury. J Neurotrauma 7:131–139

    Google Scholar 

  39. Siesjö BK (1993) Basic mechanisms of traumatic brain damage. Ann Emerg Med 22:959–969

    Google Scholar 

  40. Soffel M, Eriskat J, Plesnila M, Aggrawal N, Baethman A (1997) The penumbra zone of a traumatic cortical lesion: a microdialysis study of excitatory amino acid release. Acta Neurochir (Wien) 70:91–93

    Google Scholar 

  41. Tanaka H, Katayama Y, Kawamata T, Tsubobawa T (1994) Excitatory amino acid release from contused brain tissue in to surrounding brain areas. Acta Neurochir (Wien) 60:524–527

    Google Scholar 

  42. Uchida K, Nakakimura K, Kuroda Y, Haranishi Y, Matsumoto M, Sakabe T (2001) Dizocilpine but not Ketamine reduces the volume of ischaemic damage after acute subdural haematoma in the rat. Eur J Anaesthesiol 18:295–302

    Article  Google Scholar 

  43. Üstün ME, Gürbilek M, Ak A, Vatansever H, Duman A (2001) Effect of magnesium sulfate on tissue lactate and malondialdehyde levels in experimental head trauma. Intensive Care Med 27:264–268

    Article  Google Scholar 

  44. Vagnozzi R, Marmarou A, Tavazzi B, Signoretti S, Di Pierro D, Del Bolgia F, Amorini AM, Fazzina G, Sherkat S, Lazzarino G (1999) Changes of cerebral energy metabolism and lipid peroxidation in rats leading to mitochondrial dysfunction after diffuse brain injury. J Neurotrauma 16:903–913

    Google Scholar 

  45. Weller M, Finiels-Marlier F, Paul SM (1993) NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine. Brain Res 613:143–148

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Ataturk State Hospital, 35360, İzmir, Turkey

    Hakan Özsüer

  2. Department of Neurosurgery, School of Medicine, University of Suleyman Demirel, 32260, Isparta, Turkey

    Aşkın Görgülü

  3. Süleyman Demirel Bulvarı 101 Cadde No 73, Sener Apt A Blok Daire 5, 32100, Isparta, Turkey

    Aşkın Görgülü

  4. Department of Neurosurgery, School of Medicine, University of Istanbul, 34390, Çapa, Istanbul, Turkey

    Talat Kırış

  5. Department of Neurosurgery, School of Medicine, University of Trakya, 22030, Edirne, Turkey

    Sabahattin Çobanoğlu

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  1. Hakan Özsüer
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  2. Aşkın Görgülü
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  3. Talat Kırış
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Correspondence to Aşkın Görgülü.

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Özsüer, H., Görgülü, A., Kırış, T. et al. The effects of memantine on lipid peroxidation following closed-head trauma in rats. Neurosurg Rev 28, 143–147 (2005). https://doi.org/10.1007/s10143-004-0374-1

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