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Effects of mexiletine, ginkgo biloba extract (EGb 761), and their combination on experimental head injury

Neurosurgical Review volume 26, pages 288–291 (2003)Cite this article

Abstract

Lipid peroxidation (LP) and brain edema are important factors that produce tissue damage in head injury. The purpose of this study was to investigate the effect of mexiletine, gingko biloba extract (EGb 761), and their combination on LP and edema after moderate head trauma. Forty rats were randomly and blindly divided into four groups of ten animals each: control group (bolus injection of physiological saline), mexiletine group (50 mg/kg per injection), EGb 761 group (30 mg/kg per injection), and mexiletine plus EGb 761 group (50 mg/kg and 30 mg/kg per injection, respectively). The injections were given intraperitoneally at 1 h, 9 h, and 17 h after trauma. Twenty-four hours after injury, the rats were killed, and malondialdehyde (MDA) levels and brain water content were determined. Rats treated with mexiletine, EGb 761, and mexiletine plus EGb 761 had significantly lower MDA levels than the control group (P<0.01). The lowest MDA levels were measured in the mexiletine plus EGb 761 group. However, there was no significant difference in brain water content between treated groups and the control group (P>0.05). These findings show the usefulness of mexiletine and its combination with EGb 761 as a cerebroprotective agent in this model of experimental head injury.

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References

  1. Anderson DK, Demediuk P, Saunders RD, et al (1985) Spinal cord injury and protection. Ann Emerg Med 14:816–821

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. Benzel EC, Tator CH (1995) Contemporary management of spinal cord injury. In: Young W, Huang PP, Kume-Kick J (eds) Cellular, ionic, and biomolecular mechanisms of the injury process. American Association of Neurosurgeons, Park Ridge, pp 27–42

  4. Borzeix MG (1985) Effect of gingko biloba extract on two types of cerebral edema. In: Fünfgeld EW (ed) Effects of gingko biloba extract on organic cerebral impairment. Springer, Berlin Heidelberg New York, pp 51–56

  5. Braughler JM, Hall ED (1989) Central nervous system trauma and stroke. I. Biochemical considerations for oxygen radical formation and lipid peroxidation. Free Radic Biol Med 6:289–301

    Article  CAS  PubMed  Google Scholar 

  6. Calapai G, Crupi A, Firenzuoli F, Marciano MC, Squadrito F, Inferrera G (2000) Neuroprotective effects of gingko biloba extract in brain ischemia are mediated by inhibition of nitric oxide synthesis. Life Sci 67:2673–2683

    Article  CAS  PubMed  Google Scholar 

  7. Caner H, Kwan AL, Bavbek M, Kılınç K, Durieux M, Lee K, Kassell NF (2000) Systemic administration of mexiletine for attenuation of cerebral vasospasm following experimental subarachnoid hemorrhage. Acta Neurochir (Wien) 142:455–461

    Google Scholar 

  8. Chan PH, Schmidley JW, Fishman RA, Longar SM (1984) Brain injury, edema and vascular permeability changes induced by oxygen-derived free radicals. Neurology 34:315–320

    CAS  PubMed  Google Scholar 

  9. De Feudis FV (1991) Ginkgo biloba extract (EGb 761) pharmacological activity and clinical applications. In: Effects of Egb 761 on the CNS. Elsevier, Tokyo, pp 551–556

  10. Demirpeçe E, Caner H, Bavbek M, Kılınç K (1999) Antioxidant action of the antiarrhythmic drug mexiletine in brain membranes. Jpn J Pharmacol 81:7–11

    Article  PubMed  Google Scholar 

  11. Demopoulus HB, Flamm ES, Pietronigro DD, Seligman ML (1980) The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol Scand 492:91–119

    Google Scholar 

  12. Dohi Y, Kojima M, Sato K (1994) Vasorelaxant effect of mexiletine in mesenteric resistance arteries of rats. Br J Pharmacol 111:673–680

    CAS  PubMed  Google Scholar 

  13. Fercakova A, Halat G, Marsala M, et al (1992) Graded postischemic reoxygenation reduces lipid peroxidation and reperfusion injury in rabbit spinal cord. Brain Res 593:159–167

    Article  CAS  PubMed  Google Scholar 

  14. Fern R, Ransom BR, Stys PK, Waxman SG (1993) Pharmacological protection of CNS white matter during anoxia: actions of phenytoin, carbamazepine and diazepam. J Pharmacol Exp Ther 266:1549–1555

    CAS  PubMed  Google Scholar 

  15. Hall ED, Braughler JM (1989) Central nervous system trauma and stroke. II. Physiological and pharmacological evidence for involvement of oxygen free radicals and lipid peroxidation. Free Radic Biol Med 6:303–313

    Article  CAS  PubMed  Google Scholar 

  16. Hall ED, Braughler JM (1993) Free radicals in CNS injury. In: Waxman SG (ed) Molecular and cellular approaches to the treatment of neurological diseases. Raven, New York, pp 81–105

  17. Kamiyama T, Tanonaka K, Harada H, Nakai K, Takeo S (1995) Mexiletine and lidocaine reduce post-ischemic functional and biochemical dysfunction of perfused hearts. Eur J Pharmacol 272:2–3

    Article  Google Scholar 

  18. Kaptanoğlu E, Caner H, Sürücü S, Akbıyık F (1999) Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury. J Neurosurg 91:200–204

    CAS  PubMed  Google Scholar 

  19. Koç RK, Kurtsoy A, Paşaoğlu H, Karaküçük EI, Öktem İS, Meral M (1999) Lipid peroxidation and edema in experimental brain injury: comparison of treatment with methylprednisolone, tirilazad mesylate and vitamin E. Res Exp Med 199:21–28

    Article  Google Scholar 

  20. Kurtsoy A, Canbay S, Öktem IS, Akdemir H, Koç RK, Menkü A, Tucer B (2000) Effect of Egb-761 on vasospasm in experimental subarachnoid hemorrhage. Res Exp Med 199:207–215

    CAS  Google Scholar 

  21. Lee EJ, Ayoub IA, Harris FB, Hassan M, Ogilvy CS, Maynard KI (1999) Mexiletine and magnesium independently, but not combined, protect against permanent focal cerebral ischemia in Wistar rats. J Neurosci Res 58:442–448

    Article  CAS  PubMed  Google Scholar 

  22. Marmarou A, Foda MA, van den Brink W, et al (1994) A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 80:291–300

    CAS  PubMed  Google Scholar 

  23. Maynard KI, Kawamata T, Ogilvy CS, Perez F, Arango PM, Ames A III (1998a) Avoiding stroke during cerebral arterial occlusion by temporarily blocking neuronal functions in the rabbit. J Stroke Cerebrovasc Dis 7:287–295

    Google Scholar 

  24. 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 

  25. Otani M, Chatterjee SS, Gabard B, Kreutzberg GW (1986) Effect of an extract of gingko biloba on triethyletin induced cerebral edema. Acta Neuropathol 69:54–65

    CAS  PubMed  Google Scholar 

  26. Petty MA, Poulet P, Haas A, Namer IJ, Wagner J (1996) Reduction of traumatic brain injury-induced cerebral edema by a free radical scavenger. Eur J Pharmacol 307:149–155

    Article  CAS  PubMed  Google Scholar 

  27. Pierre S, Jamme I, Droy-Lefaix MT, Nouvelot A, Maixent JM (1999) Gingko biloba extract (EGb 761) protects Na,K-ATPase activity during cerebral ischemia in mice. Neuroreport 10:47–51

    CAS  PubMed  Google Scholar 

  28. Saunders RD, Dugan LL, Demediuk P, et al (1987) Effect of methylprednisolone and the combination of alpha-tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue. J Neurochem 49:24–31

    CAS  PubMed  Google Scholar 

  29. Seligman ML, Flamm ES, Goldstein BD, Posec RG, Demopoulos HB, Ransohoff J (1977) Spectro-fluorescent detection of malondialdehyde as a measure of lipid free radical damage in response to ethanol potentiation of spinal cord trauma. Lipids 12:945–950

    CAS  PubMed  Google Scholar 

  30. Sanada T, Nakamura T, Nishimura MC, Isayama K, Pitts LH (1993) Effect of U74006F on neurologic function and brain edema after fluid percussion injury in rats. J Neurotrauma 10:65–70

    CAS  PubMed  Google Scholar 

  31. Stein DG, Hoffman SW (1992) Chronic administration of gingko biloba extract EGb 761 can enhance recovery from traumatic brain injury. In: Effects of gingko biloba extract (EGb 761) on the central nervous system. Elsevier, Paris, pp 95–103

  32. Stys PK, Ransom BR, Waxmann SO, Davis PK (1990) Role of extracellular calcium in anoxic injury of mammalian central white matter. Proc Natl Acad Sci U S A 87:4212–4216

    CAS  PubMed  Google Scholar 

  33. Stys PK, Ransom BR, Waxmann SG (1992) Tertiary and quaternary local anesthetics protect central nervous system white matter from anoxic injury at concentrations that do not block excitability. J Neurophysiol 67:236–240

    CAS  PubMed  Google Scholar 

  34. Stys PK, Waxmann SG, Ransom BR (1992) Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na+-Ca2+ exchanger. J Neurosci 12:430–439

    CAS  PubMed  Google Scholar 

  35. Stys PK, Lesiuk H (1996) Correlation between electrophysiological effects of mexiletine and ischemic protection in CNS white matter. Neuroscience 71:27–36

    Article  CAS  PubMed  Google Scholar 

  36. Wahl M, Unterberg A, Baethmann A, Schilling L (1988) Mediators of blood-brain barrier dysfunction and formation of vasogenic brain edema. J Cereb Blood Flow Metab 8:621–634

    Google Scholar 

  37. Willmore LJ, Rubin JJ (1984) Effect of antiperoxidants on FeCL2-induced lipid peroxidation and focal edema in rat brain. Exp Neurol 83:62–70

    CAS  PubMed  Google Scholar 

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Affiliations

  1. Department of Neurosurgery, Erciyes University Medical School, 38039, Kayseri, Turkey

    Ahmet Menkü, R. Kemal Koç, Vatan Tayfur & Hidayet Akdemir

  2. Department of Biochemistry, Erciyes University Medical School, 38039, Kayseri, Turkey

    Recep Saraymen & Figen Narin

Authors
  1. Ahmet Menkü
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  2. R. Kemal Koç
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  3. Vatan Tayfur
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  4. Recep Saraymen
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  5. Figen Narin
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  6. Hidayet Akdemir
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Correspondence to Ahmet Menkü.

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Menkü, A., Koç, R.K., Tayfur, V. et al. Effects of mexiletine, ginkgo biloba extract (EGb 761), and their combination on experimental head injury. Neurosurg Rev 26, 288–291 (2003). https://doi.org/10.1007/s10143-003-0277-6

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  • DOI: https://doi.org/10.1007/s10143-003-0277-6

Keywords

  • Antioxidant
  • EGb 761
  • Head injury
  • Lipid peroxidation
  • Mexiletine