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The therapeutic value of naloxone and manitol in experimental focal cerebral ischemia

Neurological outcome, histopathological findings, and tissue concentrations of Na+, K+ and water

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Research in Experimental Medicine

Abstract

In this study, the effect of naloxone and mannitol was investigated on focal cerebral ischemia induced by middle cerebral artery occlusion with the trans-orbital approach in the rabbit model. Rabbits were randomly and blindly assigned to one of three groups (six animals in each): (1) a control group that received equal volumes of physiological saline solution; (2) a naloxone group that received a 5 mg/kg bolus of naloxone i.v. 1 h after occlusion, followed by 2 mg/kg per hour i. v. infusion for 5 h; (3) a mannitol group that received 0.2 g/kg twice with an interval of 10 min at 5 h. The neurological outcome was better in rabbits treated with naloxone than in the others. The ratio of ischemic to total neurons in the cortex was smaller in the naloxone group than in the control and mannitol groups (P<0.05). In addition, there was a statistically significance reduction in infarct size in the naloxone group compared with the other groups (P<0.05). Edema was severe in the control and mannitol groups, but moderate in the naloxone group. There was no statistically significant difference in Na+, K+, and water content between groups. Our data provide evidence for the beneficial effects of naloxone on promoting neurological recovery and preserving the ischemic area.

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References

  1. Baskin DS, Hosobuchi Y (1981) Naloxone reversal of ischemic neurological deficits in man. Lancet II:272:275

    Article  Google Scholar 

  2. Baskin DS, Kieck CF, Hosobuchi Y (1982) Naloxone reversal of ischemic neurologic deficits in baboons is not mediated by systemic effects. Life Sci 31:2201–2204

    Article  PubMed  CAS  Google Scholar 

  3. Baskin DS, Kieck CF, Hosobuchi Y (1984) Naloxone reversal and morphine exacerbation of neurologic deficits secondary to focal cerebral ischemia in baboons. Brain Res 290:289–296

    Article  PubMed  CAS  Google Scholar 

  4. Baskin DS, Hosobuchi Y, Grevel JC (1986) Treatment of experimental stroke with opiate antagonists. Effects on neurological function, infarct size, and survival. J Neurosurg 64: 99–103

    PubMed  CAS  Google Scholar 

  5. Betz AL, Ennis SR, Schielke GP (1989) Blood-brain barrier sodium transport limits development of brain edema during partial ischemia in gerbils. Stroke 20:1253–1259

    PubMed  CAS  Google Scholar 

  6. Biller J (1992) Medical management of acute cerebral ischemia. Neurol Clin 20:63–85

    Google Scholar 

  7. Bodsch W, Rommel T, Ophoff BG, Menzel J (1987) Factors responsible for the retention of fluid in human tumor edema and the effect of dexamethasone. J Neurosurg 67:250–257

    PubMed  CAS  Google Scholar 

  8. Bredesen DE, Cutler JR, Simon RP (1982) Failure of naloxone to reverse vasular neurologic deficit (abstract) Neurology 32:A 79

    Google Scholar 

  9. Brown FD, Johns L, Jafar JJ, Crockard HL, Mullan S (1979) Detailed monitoring of the effects of mannitol following experimental head injury. J Neurosurg 50:423–432

    PubMed  CAS  Google Scholar 

  10. Cote CJ, Greenbow DE, Marshal BE (1979) The hypotensive response to rapid intravenous administration of hypertonic solutions in man and in the rabbit Anesthesiology 50:30–35

    Article  PubMed  CAS  Google Scholar 

  11. Dennis RC, Harlow C, Egdahl RH, Hechtman HB (1980) Enhancement of myocardial function with glucose, insulin and potassium. Surg Gynecol Obstet 151:185–190

    PubMed  CAS  Google Scholar 

  12. Faden AI, Yum SW, Lemke M, Vink R (1990) Effect of TRH-anolog treatment on tissue cations, phospholipids and energy metabolism after spinal cord injury. J Pharmacol Exp Ther 255:608–614

    PubMed  CAS  Google Scholar 

  13. Fallis FJ, Fisher M, Lobo RA (1984) A double blind trial of naloxone in the treatment of acute stroke. Stroke 15:627–629

    PubMed  CAS  Google Scholar 

  14. Gaines C, Nehls DG, Suess BS, Waggener JD, Crowell RB (1984) Effect of naloxone on experimental stroke in awake monkeys. Neurosurgery 14:308–314

    Article  PubMed  CAS  Google Scholar 

  15. Gotoh O, Asano T, Koide T, Takakura K (1985) Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I. The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to125I-albumin. Stroke 16:101–109

    PubMed  CAS  Google Scholar 

  16. Heiss WD (1983) Flow thresholds of functional and morphological damage of brain tissue. Stroke 14:329–331

    PubMed  CAS  Google Scholar 

  17. Holaday JW, D'Amato RK (1982) Naloxone or TRH fails to improve neurologic deficits in gerbil models of ‘stroke”. Life Sci 31:385–392

    Article  PubMed  CAS  Google Scholar 

  18. Hosobuchi Y, Baskin DS, Woo SK (1982) Reversal of induced ischemic neurologic deficit in gerbils by the opiate antagonist naloxone. Science 215:69–71

    Article  PubMed  CAS  Google Scholar 

  19. Jabaily J, Davis JN (1984) Naloxone administration to patients with acute stroke. Stroke 15:36–39

    PubMed  CAS  Google Scholar 

  20. Kato H, Kogure K, Sakamote N, Watanabe T (1987) Greater disturbance of water and ion homeostasis in the periphery of experimental focal cerebral ischaemia. Exp Neurol 96: 118–126

    Article  PubMed  CAS  Google Scholar 

  21. Kökoğlu E, Güner G, Güner A (1983) Tumoral and normal brain tissue levels of zinc in man. IRCS Med Sci 11:848

    Google Scholar 

  22. Little JR (1978) Modification of acute focal ischemia by treatment with mannitol. Stroke 9:4–9

    PubMed  CAS  Google Scholar 

  23. Little JR (1978) Modification of acute focal ischemia by treatment with mannitol and high-dose dexamethasone. J Neurosurg 49:517–524

    PubMed  CAS  Google Scholar 

  24. Lyden PD, Zivin JA, Kochhar A, Mazzarella V (1988) Effects of calcium channel blockers on neurologic outcome after focal ischemia in rabbits. Stroke 19:1020–1026

    PubMed  CAS  Google Scholar 

  25. Lyeth BG, Hayes RL (1992) Cholinergic and opioid mediation of traumatic brain injury. J Neurotrauma 9 [Suppl 2]:463–474

    Google Scholar 

  26. Meyer FB, Anderson RE, Sundt TM (1986) Intracellular brain pH, indicator tissue per fusion, electroencephalography, and histology in severe and moderate focal cortical ischemia in the rabbit. J Cereb Blood Flow Metab 6:71–78

    PubMed  CAS  Google Scholar 

  27. Meyer FB, Anderson RE, Sundt TM, Yaksh TL (1987) Treatment of experimental focal cerebral ischemia with mannitol. J Neurosurg 66:109–115

    PubMed  CAS  Google Scholar 

  28. Nehls DG, Gaines C, Crowell RM (1983) Effect of naloxone in the treatment of experimental stroke in awake monkeys (abstract). Stroke 14:123

    Google Scholar 

  29. Obana WG, Pitts LH, Nishimura MC (1988) Effect of opiate antagonist on middle cerebral artery occlusion infarct in the rat. J Neurosurg 69:98–103

    Article  PubMed  CAS  Google Scholar 

  30. Obrist WD, Thompson HK Jr, Wank HS, Wilkinson WE (1975) Regional cerebral blood flow estimated by133xenon inhalation. Stroke 6:245–256

    PubMed  CAS  Google Scholar 

  31. Pietronigro DD, Hovespian M, Demopolous HB, Flamm ES (1983) Effect of naloxone on ascorbic acid loss from ischemic cerebral cortex. Presented at the 8th International Joint Conference on Stroke and Cerebral Circulation, San Diego, California, 11 February

  32. Rogers SJ, Sherman DG (1993) Pathophysiology and treatment of acute ischemic stroke. Clin Pharm 12:359–376

    PubMed  CAS  Google Scholar 

  33. Rosner JM, Coley I (1987) Cerebral perfusion pressure: a hemodynamic mechanism of mannitol and the postmannitol hemogram. Neurosurgery 21:147–156

    Article  PubMed  CAS  Google Scholar 

  34. Schuir FJ, Hossmann KA (1980) Experimental brain infarcts in cats. Stroke 11:593–601

    Google Scholar 

  35. Selçuklu A, Koç RK, Paşaoğlu H, Kandemir O, Paşaoğlu A (1993) The effect of nimodipine, mannitol and their combination on experimental cerebral ischaemia. Turkish Neurosurg 3:95–102

    Google Scholar 

  36. Sundt TM Jr, Waltz AG (1986) Experimental cerebral infarction; retro-orbital, extradural approach for occluding the middle cerebral artery. Mayo Clin Proc 41:159–168

    Google Scholar 

  37. Sutherland G, Lesiuk H, Bose R, Sima A (1988) Effect of mannitol, nimodipine and indo-methacin singly or in combination on cerebral ischemia in rats. Stroke 19:571–578

    PubMed  CAS  Google Scholar 

  38. Young W, Rappaport ZH, Calif DJ, Flamm ES (1987) Regional brain sodium, potassium and water changes in the rat middle cerebral artery occlusion model of ischemia. Stroke 18: 751–759

    PubMed  CAS  Google Scholar 

  39. Zabramski JM, Spetzler RF, Selman WR, Roessmann WR, Hershey LA, Crumine RC, Macko R (1984) Naloxone therapy during focal cerebral ischemia. Evaluation in a primate model. Stroke 15:621–627

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, School of Medicine, Erciyes University, Kayseri, Turkey

    R. K. Koç, H. Akdemir, İ. S. Öktem & A. Paşaoğlu

  2. Department of Pathology, School of Medicine, Erciyes University, Kayseri, Turkey

    O. Kandemir

  3. Department of Biochemistry, School of Medicine, Erciyes University, Kayseri, Turkey

    H. Paşaoğlu

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  1. R. K. Koç
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  2. H. Akdemir
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  4. H. Paşaoğlu
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  5. İ. S. Öktem
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  6. A. Paşaoğlu
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Koç, R.K., Akdemir, H., Kandemir, O. et al. The therapeutic value of naloxone and manitol in experimental focal cerebral ischemia. Res. Exp. Med. 194, 277–285 (1994). https://doi.org/10.1007/BF02576389

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  • DOI: https://doi.org/10.1007/BF02576389

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