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Neuroprotective Effects by Nimodipine Treatment in the Experimental Global Ischemic Rat Model: Real Time Estimation of Glutamate

  • Choi, Seok-Keun (Department of Neurosurgery, School of Medicine, Kyung Hee University) ;
  • Lee, Gi-Ja (Department of Biomedical Engineering, School of Medicine, Kyung Hee University) ;
  • Choi, Sam-Jin (Department of Biomedical Engineering, School of Medicine, Kyung Hee University) ;
  • Kim, Youn-Jung (Department of Basic Nursing Science, School of Nursing Science, Kyung Hee University) ;
  • Park, Hun-Kuk (Department of Biomedical Engineering, School of Medicine, Kyung Hee University) ;
  • Park, Bong-Jin (Department of Neurosurgery, School of Medicine, Kyung Hee University)
  • Received : 2010.08.03
  • Accepted : 2010.12.31
  • Published : 2011.01.28

Abstract

Objective: Glutamate is a key excitatory neurotransmitter in the brain, and its excessive release plays a key role in the development of neuronal injury. In order to define the effect of nimodipine on glutamate release, we monitored extracellular glutamate release in real-time in a global ischemia rat model with eleven vessel occlusion. Methods: Twelve rats were randomly divided into two groups: the ischemia group and the nimodipine treatment group. The changes of extracellular glutamate level were measured using microdialysis amperometric biosensor, in coincident with cerebral blood flow (CBF) and electroencephalogram. Nimodipine (0.025 ${\mu}g$/100 gm/min) was infused into lateral to the CBF probe, during the ischemic period. Also, we performed Nissl staining method to assess the neuroprotective effect of nimodipine. Results: During the ischemic period, the mean maximum change in glutamate concentration was $133.22{\pm}2.57\;{\mu}M$ in the ischemia group and $75.42{\pm}4.22\;{\mu}M$ (p<0.001) in the group treated with nimodipine. The total amount of glutamate released was significantly different (P<0.001) between groups during the ischemic period. The %cell viability in hippocampus was $47.50{\pm}5.64$ (p<0.005) in ischemia group, compared with sham group. But, the %cell viability in nimodipine treatment group was $95.46{\pm}6.60$ in hippocampus (p<0.005). Conclusion: From the real-time monitoring and Nissl staining results, we suggest that the nimodipine treatment is responsible for the protection of the neuronal cell death through the suppression of extracellular glutamate release in the 11-VO global ischemia model of rat.

Keywords

References

  1. Alps BJ : Drugs acting on calcium channels : potential treatment for ischaemic stroke. Br J Clin Pharmacol 34 : 199-206, 1992 https://doi.org/10.1111/j.1365-2125.1992.tb04125.x
  2. Andine P, Orwar O, Jacobson I, Sandberg M, Hagberg H : Changes in extracellular amino acids and spontaneous neuronal activity during ischemia and extended reflow in the CA1 of the rat hippocampus. J Neurochem 57 : 222-229, 1991 https://doi.org/10.1111/j.1471-4159.1991.tb02119.x
  3. Baldwin HA, Williams JL, Snares M, Ferreira T, Cross AJ, Green AR : Attenuation by chlormethiazole administration of the rise in extracellular amino acids following focal ischaemia in the cerebral cortex of the rat. Br J Pharmacol 112 : 188-194, 1994 https://doi.org/10.1111/j.1476-5381.1994.tb13050.x
  4. Bullock R, Zauner A, Woodward JJ, Myseros J, Choi SC, Ward JD, et al. : Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg 89 : 507-518, 1998 https://doi.org/10.3171/jns.1998.89.4.0507
  5. Bullock R, Zauner A, Woodward J, Young HF : Massive persistent release of excitatory amino acids following human occlusive stroke. Stroke 26 : 2187-2189, 1995 https://doi.org/10.1161/01.STR.26.11.2187
  6. Calo G, Sbrenna S, Bianchi C, Beani L : Immediate and delayed effects of in vitro ischemia on glutamate efflux from guinea-pig cerebral cortex slices. Brain Res 751 : 300-306, 1997 https://doi.org/10.1016/S0006-8993(96)01425-4
  7. Caron MJ, Hovda DA, Becker DP : Changes in the treatment of head injury. Neurosurg Clin N Am 2 : 483-491, 1991
  8. Caragine LP, Park HK, Diaz FG, Phillis JW : Real-time measurement of ischemia-evoked glutamate release in the cerebral cortex of four and eleven vessel rat occlusion models. Brain Res 793 : 255-264, 1998 https://doi.org/10.1016/S0006-8993(98)00182-6
  9. Chapman AG, Halsey MJ, Hart GP, Luff NP, Meldrum BS, Wardley-Smith B : Regional amino acid concentration in the brains of rats exposed to high pressures. J Neurochem 47 : 314-317, 1986
  10. Choi DW : Glutamate neurotoxicity and diseases of the nervous system. Neuron 1 : 623-634, 1988 https://doi.org/10.1016/0896-6273(88)90162-6
  11. Choi DW, Rothman SM : The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13 : 171-182, 1990 https://doi.org/10.1146/annurev.ne.13.030190.001131
  12. Choi S, Kang SW, Lee GJ, Choi SK, Chae SJ, Park HK, et al. : Real-time ischemic condition monitoring in normoglycemic and hyperglycemic rats. Physiol Meas 31 : 439-450, 2010 https://doi.org/10.1088/0967-3334/31/3/011
  13. Choi S, Lee GJ, Chae SJ, Kang SW, Yin CS, Lee SH, et al. : Potential neuroprotective effects of acupuncture stimulation on diabetes mellitus in a global ischemic rat model. Physiol Meas 31 : 633-647, 2010 https://doi.org/10.1088/0967-3334/31/5/003
  14. Dirnagl U, Jacewicz M, Pulsinelli W : Nimodipine posttreatment does not increase blood flow in rats with focal cortical ischemia. Stroke 21 : 1357-1361, 1990 https://doi.org/10.1161/01.STR.21.9.1357
  15. Drejer J, Benveniste H, Diemer NH, Schousboe A : Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J Neurochem 45 : 145-151, 1985 https://doi.org/10.1111/j.1471-4159.1985.tb05486.x
  16. Estevez AY, O'Regan MH, Song D, Phillis JW : Effects of anion channel blockers on hyposmotically induced amino acid release from the in vivo rat cerebral cortex. Neurochem Res 24 : 447-452, 1999 https://doi.org/10.1023/A:1020902104056
  17. Feinberg WM, Bruck DC : Effect of oral nimodipine on platelet function. Stroke 24 : 10-13, 1993 https://doi.org/10.1161/01.STR.24.1.10
  18. Fujisawa A, Matsumoto M, Matsuyama T, Ueda H, Wanaka A, Yoneda S, et al. : The effect of the calcium antagonist nimodipine on the gerbil model of experimental cerebral ischemia. Stroke 17 : 748-752, 1986 https://doi.org/10.1161/01.STR.17.4.748
  19. Guyot LL, Diaz FG, O'Regan MH, Song D, Phillis JW : The effect of streptozotocin-induced diabetes on the release of excitotoxic and other amino acids from the ischemic rat cerebral cortex. Neurosurgery 48 : 385-390, 2001
  20. Huang SJ, Chang L, Han YY, Lee YC, Tu YK : Efficacy and safety of hypertonic saline solutions in the treatment of severe head injury. Surg Neurol 65 : 539-546, 2006 https://doi.org/10.1016/j.surneu.2005.11.019
  21. Katayama Y, Becker DP, Tamura T, Hovda DA : Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg 73 : 889-900, 1990 https://doi.org/10.3171/jns.1990.73.6.0889
  22. Katayama Y, Kawamata T, Tamura T, Hovda DA, Becker DP, Tsubokawa T : Calcium-dependent glutamate release concomitant with massive potassium flux during cerebral ischemia in vivo. Brain Res 558 : 136-140, 1991 https://doi.org/10.1016/0006-8993(91)90730-J
  23. Koura SS, Doppenberg EM, Marmarou A, Choi S, Young HF, Bullock R : Relationship between excitatory amino acid release and outcome after severe human head injury. Acta Neurochir Suppl 71 : 244-246, 1998
  24. Krieglstein J, Lippert K, Poch G : Apparent independent action of nimodipine and glutamate antagonists to protect cultured neurons against glutamate-induced damage. Neuropharmacology 35 : 1737-1742, 1996 https://doi.org/10.1016/S0028-3908(96)00104-9
  25. Kulik A, Trapp S, Ballanyi K : Ischemia but not anoxia evokes vesicular and Ca(2+)-independent glutamate release in the dorsal vagal complex in vitro. J Neurophysiol 83 : 2905-2915, 2000 https://doi.org/10.1152/jn.2000.83.5.2905
  26. Lazarewicz JW, Pluta R, Puka M, Salinska E : Diverse mechanisms of neuronal protection by nimodipine in experimental rabbit brain ischemia. Stroke 21 : IV108-IV110, 1990
  27. Lee GJ, Choi SK, Eo YH, Kang SW, Choi S, Park JH, et al. : The effect of extracellular glutamate release on repetitive transient ischemic injury in global ischemia model. Korean J Physiol Pharmacol 13 : 23-26, 2009 https://doi.org/10.4196/kjpp.2009.13.1.23
  28. Lee SR, Lok J, Rosell A, Kim HY, Murata Y, Atochin D, et al. : Reduction of hippocampal cell death and proteolytic responses in tissue plasminogen activator knockout mice after transient global cerebral ischemia. Neuroscience 150 : 50-57, 2007 https://doi.org/10.1016/j.neuroscience.2007.06.029
  29. Limbrick DD Jr, Sombati S, DeLorenzo RJ : Calcium influx constitutes the ionic basis for the maintenance of glutamate-induced extended neuronal depolarization associated with hippocampal neuronal death. Cell Calcium 33 : 69-81, 2003 https://doi.org/10.1016/S0143-4160(02)00054-4
  30. Marcoli M, Bonfanti A, Roccatagliata P, Chiaramonte G, Ongini E, Raiteri M, et al. : Glutamate efflux from human cerebrocortical slices during ischemia : vesicular-like mode of glutamate release and sensitivity to A(2A) adenosine receptor blockade. Neuropharmacology 47 : 884-891, 2004 https://doi.org/10.1016/j.neuropharm.2004.06.022
  31. Matsumoto M, Scheller MS, Zornow MH, Strnat MA : Effect of S-emopamil, nimodipine, and mild hypothermia on hippocampal glutamate concentrations after repeated cerebral ischemia in rabbits. Stroke 24 : 1228-1234, 1993 https://doi.org/10.1161/01.STR.24.8.1228
  32. Milde LN, Milde JH, Michenfelder JD : Delayed treatment with nimodipine improves cerebral blood flow after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 6 : 332-337, 1986 https://doi.org/10.1038/jcbfm.1986.56
  33. Miljanich GP, Ramachandran J : Antagonists of neuronal calcium channels : structure, function, and therapeutic implications. Annu Rev Pharmacol Toxicol 35 : 707-734, 1995 https://doi.org/10.1146/annurev.pa.35.040195.003423
  34. Morley P, Hogan MJ, Hakim AM : Calcium-mediated mechanisms of ischemic injury and protection. Brain Pathol 4 : 37-47, 1994
  35. Muir KW, Lees KR : Excitatory amino acid antagonists for acute stroke. Cochrane Database Syst Rev CD001244, 2003
  36. Nakane H, Ooboshi H, Ibayashi S, Yao H, Sadoshima S, Fujishima M : Isradipine, a calcium channel blocker, attenuates the ischemia-induced release of dopamine but not glutamate in rats. Neurosci Lett 188 : 151-154, 1995 https://doi.org/10.1016/0304-3940(95)11417-U
  37. Siesjo BK, Bengtsson F : Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression : a unifying hypothesis. J Cereb Blood Flow Metab 9 : 127-140, 1989 https://doi.org/10.1038/jcbfm.1989.20
  38. Steen PA, Newberg LA, Milde JH, Michenfelder JD : Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 3 : 38-43, 1983 https://doi.org/10.1038/jcbfm.1983.4
  39. Terrian DM, Dorman RV, Gannon RL : Characterization of the presynaptic calcium channels involved in glutamate exocytosis from rat hippocampal mossy fiber synaptosomes. Neurosci Lett 119 : 211-214, 1990 https://doi.org/10.1016/0304-3940(90)90836-X
  40. Van Harreveld A, Fifkova E : Mechanisms involved in spreading depression. J Neurobiol 4 : 375-387, 1973 https://doi.org/10.1002/neu.480040406
  41. Wahl F, Obrenovitch TP, Hardy AM, Plotkine M, Boulu R, Symon L : Extracellular glutamate during focal cerebral ischaemia in rats : time course and calcium dependency. J Neurochem 63 : 1003-1011, 1994
  42. Welsch M, Nuglisch J, Krieglstein J : Neuroprotective effect of nimodipine is not mediated by increased cerebral blood flow after transient forebrain ischemia in rats. Stroke 21 : IV105-IV107, 1990
  43. Yi JH, Hazell AS : Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem Int 48 : 394-403, 2006 https://doi.org/10.1016/j.neuint.2005.12.001
  44. Yin CS, Choi SK, Lee GJ, Eo YH, Kim BS, Oh BS, et al. : A real-time glutamate release in rat striatum of 11-vessel-occlusion ischemia model treated with acupuncture. Korean J Orient Physiol Pathol 22 : 835-840, 2008
  45. Ziskin JL, Nishiyama A, Rubio M, Fukaya M, Bergles DE : Vesicular release of glutamate from unmyelinated axons in white matter. Nat Neurosci 10 : 321-330, 2007 https://doi.org/10.1038/nn1854

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