Protective Effects of Stephania tetrandra against Focal Cerebral Ischemic Damage by Middle Cerebral Artery Occlusion in Rats

방기가 백서 중대뇌동맥 폐쇄에 의한 국소뇌허혈손상에 미치는 보호효과

  • 정혁상 (경희대학교 동서의학대학원 신경과학교실) ;
  • 이현삼 (경희대학교 동서의학대학원 신경과학교실) ;
  • 원란 (경희대학교 동서의학대학원 신경과학교실) ;
  • 강철훈 (경희대학교 동서의학대학원 신경과학교실) ;
  • 손낙원 (경희대학교 동서의학대학원 신경과학교실)
  • Published : 2001.03.01

Abstract

Objective : This study was performed to investigate the protective effect of Stephania tetrandra(ST) against ischemic brain damage after a middle cerebral artery(MCA) occlusion. The effect was evaluated using histological tests, neurobehavioral tests, and biochemical tests. Methods : Rats(Sprague-Dawley) were divided into four groups : sham operated group, MCA occluded group, post MCA occlusion Stephania tetrandra administrated (7.6mg/l00g) group, and normal group. The MCA was occluded by intraluminal method. Stephania tetrandra was administrated orally twice at 1 and 4 hours after MCA occlusion. The neurobehavioral test was performed at 3, 6, 9 and 24 hours after MCA occlusion by posture reflex test and swimming behavioral test. All groups were sacrificed then. The brain tissues were stained with 2% triphenyl tetrazolium chloride(TTC) or 1 % cresyl violet solution, to examine infarct size, volume and cell number. Tumor necrosis $factor-{\alpha}$ level was measured from sera using Enzyme-Linked Immunoabsorbent Assay(ELISA). The mRNA expression level of inflammatory cytokines and related receptor type I and II, $IL-1{\beta}$, IL-6, and IL-10 6hours after MCA occlusion were also studied by reverse transcriptase polymerase chain reaction(RTPCR). Results : The results showed that : Stephania tetrandra (1) reduced infarct size and total infarct volume by 52.2% compared to the control group; (2) attenuated significantly in neuronal death, which was shown by a decrease in cell number(P<0.01) and size(P<0.01) in the boundary area of the infarction; (3) significantly reduced serum $TNF-{\alpha}$ level, and increased the mRNA level of IL-10 in the cortex region(P<0.01). However, there was no significant effect on motor deficit in swimming behavioral test. Conclusions : In conclusion, Stephania tetrandra has protective effects against ischemic brain damage at the early stage of ischemia.

Keywords

References

  1. Neuron v.1 Glutamate neurotoxicity and diseases of the nervous system Choi, D.W.
  2. Neurochemistry v.9 Reduction fo neural damage in irreversible cerebral ischemia by calcium antagonists Sauter, A.;Rudin, M.;Wiederhold, K.H.
  3. Brain Res. v.492 Ischemia triggers NMDA receptor-linked cytoskeletal proteolusis in hippocampus Seubert, P.;Lee, K.;Lynch, G.
  4. J. Neurosurg v.69 Effect of opiate antagonists on middle cerebral artery occlusion infarct in the rat Obana, W.G.;Pitts, L.H.;Nishimura, M.C.
  5. J Cereb blood Metab v.9 Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression:a unifying hypothesis Siesjo, B.K.;Bengtsson, F.
  6. 本草學 李尙仁
  7. Planta Med. v.65 no.2 Acute hemodynamic effects of tetramethylpyrazine and tetrandrine on cirrhotic rats Huang YT;Chang FC;Chen KJ;Hong CY
  8. J Ethnopharmacol v.66 no.2 Effects of tetrandrine and fangchinoline on human platelet aggregation and thromboxane B2 formation Kim, H.S.;Zhang, Y.H.;Fang, L.H.;Yun, Y.P.;Lee, H.K.
  9. Naunyn Schmiedebergs Arch Pharmacol. v.357 no.4 Blockade of voltage-operated calcium channels, increase in spontaneous catecholamine release and elevation of intracellular calcium levels in bovine chromaffin cells by the plant alkaloid tetrandrine Bickmeyer, U.;Weinsberg, F.;Muller, E.;Wiegand, H.
  10. Neuropharmacology v.33 no.7 Effects of tetrandrine on calcium channel currents of bovine chromaffin cells Weinsberg, F.;Bickmeyer, U.;Wiegand, H.
  11. Stroke v.23 Neurological and Behavioral Outcomes of Focal Cerebral Ischemia in Rats Florence, W.;Monique, A.;Michel, P.;Roger, G.
  12. Stroke v.20 Reversible middles cerebral artery occlusion without craiectomy in rats Zea Longa, E.L.;Weinstein, P.R.;Carlson, S.;Cummins, R.
  13. Stroke v.27 Middle cerebral artery occlusion in the rat by intraluminal sutrue Belayev, L.;Alonso, O.F.;Busto, R.;Zhao, W.;Ginsberg, M.D.
  14. The Rat Brain George, P.;Charles, W.
  15. J Crerb Blood Flow Metab v.10 no.2 A semiautomated method for measuring brain infarct volume Swanson, R.A.;Morton, M.T.;Tsao Wu, G.;Savalos, R.A.;Davidson, C.;Sharp, F.R.
  16. Learning and Motivation v.12 Special localization does not require the presence of local cues Morris, R.G.M.
  17. Stroke v.17 Rat middle cerebral artery occlusion:Evaluation of the model and development of a neurologic examination Bederson, J.B.;Pitts, L.H.;Tsuji, M.;Nishimura, M.C.;David, R.L.;Bartkowski, H.
  18. Clin Exp Pharmacol Physiol. v.23 no.8 Effects of tetrandrine and closely related bis-benzylisoquinoline derivatives on cytosolic $Ca^{2+}$ in hyman leukaemic HL-60 cells:a structure-activity relationship study Leung, Y.M.;Berdik, M.;Kwan, C.Y.;Loh, T.T.
  19. Int Arch Allergy Appl Immunol v.85 no.4 In vitro immunosuppressive properties of the plant alkaloid tetrandrine Seow, W.K.;Ferrante, A.;Goh, D.B.;Chalmers, A.H.;Li, S.Y.;Thong, Y.H.
  20. Journal of cerebral blood flow and metabolism v.18 no.1 Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury Sean, D.L.;Florence, M.H.;Berislav, V.Z.
  21. Jornal cerebral blood flow and metabolism v.19 no.6 Neuroflament proteolysis after focal sichemia When docells die after experimental stroke? Aronowski, J.;Cho, K.H.;Storng, R.;Grotta, J.
  22. Stroke v.20 Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion Nagasawa, H.;Kogure, K.
  23. Stroke v.20 Neuronal necrosis after middle cerebral artery occlusion in wistar rats progresses at different time intervals in the caudoputamen and the cortex Garcia, J.H.;Kai Feng.;Ho, K.L.
  24. Physical Rev. v.79 no.4 Ischemic cell death in brain neurons Lipton, P.
  25. Cerebrovasc Brain Metab Rev. v.6 no.4 Cytokines,inflammation, and brain injury:role of tumor necrosis factor-alpha Feuerstein, G.Z.;Liu, T.;Barone, F.C.
  26. J Cereb Blood vlow Metab. v.18 no.2 Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat Loddick, S.A.;Turnbull, A.V.;Rothwell, N.J.
  27. Eur J Neurosci v.12 no.7 Interleukin-10 modulates neuronal threshold of vulnerability to ischemic damage Grilli, M.;Barbieri, I.;Basudev, H.;Brusa, R.;Casati, C.;Lozza, G.;Ongini, E.
  28. Shock v.8 no.5 Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia Botchkina, G.I.;Wang, H.;Di Santo E.;Cockroft, K.M.;Bloom, O.;Vishnubhakat, J.M.;Ghezzi, P.;Tracey, K.J.
  29. Mol Med. v.3 no.11 Expression of TNF and TNF receptors(p55 and p75) in the rat brain after focal cerebral ischemia Blochkina, G.I.;Meistrell, M.E.;Botchkina, I.L.;Tracey, K.J.
  30. Neuroscience v.71 no.1 Expressiong of tumor necrosis factor alpha focal cerebral ischemia in the rat Buttini, M.;Appel, K.;Sauter, A.;Gebicke Haerter, P.J.;Boddeke, H.W.
  31. Stroke v.25 Tumor recrosis factor-$\alpha$ expression in ischemic neurons Liu, T.;Clark, R.K.;McDonnell, P.C.;Young, P.R.;White, R.F.;Barone, F.C.;Feuerstein, G.Z.
  32. Proc Natl Acad Sci. v.92 Tumor necrosis factors $\alpha$ and $\beta$protect neurons against amyloid $\beta$-peptide toxicity;evidience for involvement of a $\kappa$B-bind factor and attenuation of peroxide $Ca^{2+}$ accumulation Barger, S.Q.;Horster, D.;Furukawa, K.;Goodman, Y.;Krieglstein, J.;Mattson, M.
  33. Journal of cerebral blood flow and metabolism v.17 no.2 Inibition of tumor necrosis factor and amelioration of brain infarction in mice Nawashiro, H.;Martin, D.;Hallenbeck, J.M.
  34. Neuroreport v.9 no.9 Inhibiton of TNFalpha attenuates infarct volume and ICAM-1 expression in ischemic mouse brain Yang, G.Y.;Gong, C.;Qin, Z.;Ye, W.;Mzo, Y.;Bertz, A.L.
  35. Shock v.8 no.5 Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia Meistrell, M.E.;Botchkina, G.I.;Wang, H.;Di Santo, E.;Cockrott, K.M.;Bloom, O.;Vishubhakat, M.;Ghezzi, P.;Tracey ,K.J.
  36. Stroke v.28 Tumor Necrosis Factor-$\alpha$;A mediator of focal ischemic brain injury Barone, F.C.;Arvin, B.;White, F.;Miller, A.;Webb, C.L.;Willette, R.N.;Lysko, P.G.;Feuerstein, G.Z.
  37. J Cereb Blood Flow Metab v.17 no.5 Induction of tumor necrosis factor-alpha in the mouse hippocampus following transient forebrain ischemia Uno, H.;Matsuyama, T.;Akita, H.;Nishimura, H.;Sugita, M.
  38. J Neurosci. v.19 no.9 Upregulation of tumor necrosis factor alpha transport across the blood-brain barrier after acute compressive spinal cord injury Pan, W.;Kastin, A.J.;Bell, R.L.;Olson, R.D.
  39. J Neuroimmunol. v.22;109 no.2 Role of NMDA receptor signaling in the regulation of inflammatory gene expression after focal brain ischemia Jander, S.;Schroeter, M.;Stoll, G.
  40. J Ethnopharmacol. v.69 no.2 Anti-inflammatory effects of fangchinoline and tetrandrine Choi, H.S.;Kim, H.S.;Min, K.R.;Kim, Y.;Lim, H.K.;Chang, Y.K.;Chung, M.W.