The Korea Journal of Herbology (대한본초학회지)

The Korea Association of Herbology (대한본초학회)
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Sesamin attenuates neuronal damage through inhibition of microglial activation following global cerebral ischemia in rats

  • Kong, Minjung (Department of Herbal Pharmacology, College of Oriental Medicine, Kyung Hee University) ;
  • Hong, Sung In (Department of Herbal Pharmacology, College of Oriental Medicine, Kyung Hee University)
  • Received : 2013.02.23
  • Accepted : 2013.03.21
  • Published : 2013.03.30
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Abstract

Objectives : Sesamin, a major lignan in sesame seeds, has been reported to have neuroprotective effects against in vitro ischemia and in vivo MCAo-reperfusion cerebral ischemia model, however, there is no reports in an in vivo global cerebral ischemia model. The purpose of the study was to investigate the neuroprotective effect of sesamin in global cerebral ischemia induced by four-vessel occlusion (4-VO) in rats through inhibition of microglial activation in this model. Methods : The neuroprotective effects were investigated using a 10 min of 4-VO ischemia rat model by measuring intact pyramidal neurons in the CA1 region of the hippocampus using Nissle staining. The antiinflammatory or reducing neurotoxicity effect was investigated using immunohistochemisty, RT-PCR and western blot analysis of inflammatory or neurotoxic mediators. Results : Intraperitoneal injection of sesamin at doses of 0.3, 1.0, 3.0, and 10.0 mg/kg at 0 min and 90 min after ischemia conferred 26.6%, 30.1%, 42.5%, and 30.5% neuroprotection, respectively, compared to the vehicle-treated control group. A 3.0 mg/kg dose of sesamin inhibited microglia activation and consequently, cyclooxygenase-2, inducible nitric oxide, and interleukine-$1{\beta}$ expressions at 48 h after reperfusion. Conclusions : Sesamin protects neuronal cell death through inhibition of microglial activation or the production of neurotoxic metabolites and proinflammatory mediators by microglia such as COX-2, iNOS and IL-$1{\beta}$ in global cerebral ischemia.

Keywords

References

  1. Park SH, Ryu SN, Bu Y, Kim H, Simon JE, Kim KS. Antioxidants components as potential neuroprotective agents in sesame (Sesamum indicum L.). Food Rev Int. 2010 ; 26 : 103-21. https://doi.org/10.1080/87559120903564464
  2. Ryu SR, Lee JI, Kang SS, Choi CY. Quantitative analysis of antioxidants in Sesame seed. Korean J Crop Sci. 1992 ; 37 : 377-82.
  3. Cooney RV, Custer LJ, Okinaka L, Franke AA. Effects of dietary sesame seeds on plasma tocopherol levels. Nutr Cancer. 2001 ; 39 : 66-71. https://doi.org/10.1207/S15327914nc391_9
  4. Khan MM, Ishrat T, Ahmad A, Hoda MN, Khan MB, Khuwaja G, Srivastava P, Raza SS, Islam F, Ahmad S. Sesamin attenuates behavioral, biochemical and histological alterations induced by reversible middle cerebral artery occlusion in the rats. Chem Biol Interact. 2010 ; 183 : 255-63. https://doi.org/10.1016/j.cbi.2009.10.003
  5. Ohnishi M, Monda A, Takemoto R, Matsuoka Y, Kitamura C, Ohashi K, Shibuya H, Inoue A. Sesamin suppresses activation of microglia and p44/42 MAPK pathway, which confers neuroprotection in rat intracerebral hemorrhage. Neurosci. 2013 ; 232 : 45-52. https://doi.org/10.1016/j.neuroscience.2012.11.057
  6. Hou RC, Huang HM, Tzen JT, Jeng KC. Protective effects of sesamin and sesamolin on hypoxic neuronal and PC12 cells. J Neurosci Res. 2003b ; 74 : 123-33. https://doi.org/10.1002/jnr.10749
  7. Hou RC, Chen HL, Tzen JT, Jeng KC. Effect of sesame antioxidants on LPS-induced NO production by BV2 microglial cells. Neuroreport . 2003a ; 14 : 1815-9. https://doi.org/10.1097/00001756-200310060-00011
  8. Jeng KC, Hou RC, Wang JC, Ping LI. Sesamin inhibits lipopolysaccharide-induced cytokine production by suppression of p38 mitogen-activated protein kinase and nuclear factor-kappaB. Immunol Lett. 2005 ; 97 : 101-6. https://doi.org/10.1016/j.imlet.2004.10.004
  9. Petito CK, Feldmann E, Pulsinelli WA, Plum F. Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology. 1987 ; 37 : 1281-6. https://doi.org/10.1212/WNL.37.8.1281
  10. Pulsinelli WA, Brierley JB, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol. 1982 ; 11 : 491-8. https://doi.org/10.1002/ana.410110509
  11. Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 1982 ; 239 : 57-69. https://doi.org/10.1016/0006-8993(82)90833-2
  12. Nitatori T, Sato N, Waguri S, Karasawa Y, Araki H, Shibanai K, Kominami E, Uchiyama Y. Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci. 1995 ; 15 : 1001-11.
  13. Niwa M, Hara A, Iwai T, Wang S, Hotta K, Mori H, Uematsu T. Caspase activation as an apoptotic evidence in the gerbil hippocampal CA1 pyramidal cells following transient forebrain ischemia. Neurosci Lett. 2001 ; 300 : 103-6. https://doi.org/10.1016/S0304-3940(01)01559-2
  14. Pulsinelli WA, Brierley JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke. 1979 ; 10 : 267-72. https://doi.org/10.1161/01.STR.10.3.267
  15. Furlow TW, Jr.. Cerebral ischemia produced by four-vessel occlusion in the rat: a quantitative evaluation of cerebral blood flow. Stroke. 1982 ; 13 : 852-5. https://doi.org/10.1161/01.STR.13.6.852
  16. Stephenson DT, Schober DA, Smalstig EB, Mincy RE, Gehlert DR, Clemens JA. Peripheral benzodiazepine receptors are colocalized with activated microglia following transient global forebrain ischemia in the rat. J Neurosci. 1995 ; 15 : 5263-74.
  17. Ladeby R, Wirenfeldt M, Garcia-Ovejero D, Fenger C, ssing-Olesen L, Dalmau I, Finsen B. Microglial cell population dynamics in the injured adult central nervous system. Brain Res Brain Res Rev. 2005 ; 48 : 196-206. https://doi.org/10.1016/j.brainresrev.2004.12.009
  18. Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK. Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol. 1992 ; 149 : 2736-41.
  19. McMillian MK, Vainio PJ, Tuominen RK. Role of protein kinase C in microglia-induced neurotoxicity in mesencephalic cultures. J Neuropathol Exp Neurol. 1997 ; 56 : 301-7. https://doi.org/10.1097/00005072-199703000-00009
  20. Choi SH, Joe EH, Kim SU, Jin BK. Thrombin-induced microglial activation produces degeneration of nigral dopaminergic neurons in vivo. J Neurosci. 2003 ; 23 : 5877-86.
  21. Nakayama M, Uchimura K, Zhu RL, Nagayama T, Rose ME, Stetler RA, Isakson PC, Chen J, Graham SH. Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia. Proc Natl Acad Sci U S A. 1998 ; 95 : 10954-9. https://doi.org/10.1073/pnas.95.18.10954
  22. Nogawa S, Zhang F, Ross ME, Iadecola C. Cyclo-oxygenase-2 gene expression in neurons contributes to ischemic brain damage. J Neurosci. 1997 ; 17 : 2746-55.
  23. Koistinaho J, Koponen S, Chan PH. Expression of cyclooxygenase-2 mRNA after global ischemia is regulated by AMPA receptors and glucocorticoids. Stroke. 1999 ; 30 : 1900-5. https://doi.org/10.1161/01.STR.30.9.1900
  24. Dore S, Otsuka T, Mito T, Sugo N, Hand T, Wu L, Hurn PD, Traystman RJ, Andreasson K. Neuronal overexpression of cyclooxygenase-2 increases cerebral infarction. Ann Neurol. 2003 ; 54 : 155-62. https://doi.org/10.1002/ana.10612
  25. Iadecola C, Niwa K, Nogawa S, Zhao X, Nagayama M, Araki E, Morham S, Ross ME. Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc Natl Acad Sci U S A. 2001 ; 98 : 1294-9. https://doi.org/10.1073/pnas.98.3.1294
  26. Tominaga T, Sato S, Ohnishi T, Ohnishi ST. Potentiation of nitric oxide formation following bilateral carotid occlusion and focal cerebral ischemia in the rat: in vivo detection of the nitric oxide radical by electron paramagnetic resonance spin trapping. Brain Res. 1993 ; 614 : 342-6. https://doi.org/10.1016/0006-8993(93)91053-U
  27. Samdani AF, Dawson TM, Dawson VL. Nitric oxide synthase in models of focal ischemia. Stroke. 1997 ; 28 : 1283-8. https://doi.org/10.1161/01.STR.28.6.1283
  28. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 ; 87 : 1620-4. https://doi.org/10.1073/pnas.87.4.1620
  29. Iadecola C, Zhang F, Xu X. Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage. Am J Physiol. 1995 ; 268 : R286-92.
  30. Bal-Price A, Brown GC. Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci. 2001 ; 21 : 6480-91.
  31. Munch G, Gasic-Milenkovic J, Dukic-Stefanovic S, Kuhla B, Heinrich K, Riederer P, Huttunen HJ, Founds H, Sajithlal G. Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Exp Brain Res. 2003 ; 150 : 1-8. https://doi.org/10.1007/s00221-003-1389-5
  32. Schubert P, Rudolphi K. Interfering with the pathologic activation of microglial cells and astrocytes in dementia. Alzheimer Dis Assoc Disord. 1998 ; 12 Suppl 2 : S21-8.
  33. Rothwell N. Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential. Brain Behav Immun. 2003 ; 17 : 152-7. https://doi.org/10.1016/S0889-1591(02)00098-3
  34. Liu T, McDonnell PC, Young PR, White RF, Siren AL, Hallenbeck JM, Barone FC, Feurestein GZ. Interleukin-1 beta mRNA expression in ischemic
  35. Buttini M, Sauter A, Boddeke HW. Induction of interleukin-1 beta mRNA after focal cerebral ischaemia in the rat. Brain Res Mol Brain Res. 1994 ; 23 : 126-34. https://doi.org/10.1016/0169-328X(94)90218-6
  36. Berti R, Williams AJ, Moffett JR, Hale SL, Velarde LC, Elliott PJ, Yao C, Dave JR, Tortella FC. Quantitative real-time RT-PCR analysis of inflammatory gene expression associated with ischemia-reperfusion brain injury. J Cereb Blood Flow Metab. 2002 ; 22 : 1068-79. https://doi.org/10.1097/00004647-200209000-00004