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Effects of Salviae Miltiorrhizae Radix on Blood-Brain Barrier Impairment of ICH-Induced Rats

단삼(丹蔘)이 뇌조직출혈 흰쥐의 혈액뇌관문 손상에 미치는 영향

  • Park, Chang-Hoon (Department of Anatomy-Pointology, College of Oriental Medicine, Gachon University) ;
  • Kim, Youn-Sub (Department of Anatomy-Pointology, College of Oriental Medicine, Gachon University)
  • 박창훈 (가천대학교 한의과대학 해부경혈학교실) ;
  • 김연섭 (가천대학교 한의과대학 해부경혈학교실)
  • Received : 2013.12.10
  • Accepted : 2014.01.16
  • Published : 2014.01.30

Abstract

Objectives : This study was performed in order to evaluate the effects of Salviae Miltiorrhizae Radix (SMR) water extract against the cerebral hemorrhage and the blood-brain barrier (BBB) impairment in the intracerebral hemorrhage (ICH). Method : ICH was induced by the stereotaxic intrastriatal injection of bacterial collagenase type IV in Sprague-Dawley rats. SMR was orally given three times every 20 hours during 3 days after the ICH induction. Hematoma volume, water content of brain tissue and volume of evans blue leakage were examined. Myeloperoxidase (MPO) positive neutrophils and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were observed with immunofluorescence labeling and confocal microscope. Results : SMR significantly reduced the hematoma volume of the ICH-induced rat brain. SMR significantly reduced the water content of brain tissue of the ICH-induced rat brain. SMR reduced the percentage of the evans blue leakage around the hematoma on the caudate putamen compared to the ICH group, especially on the cerebral cortex. SMR significantly reduced the volume of the evans blue leakage level in the peri-hematoma regions of the ICH-induced rat brain. SMR significantly reduced MPO positive neutrophils in the peri-hematoma regions of the ICH-induced rat brain. SMR reduced the TNF-${\alpha}$ expression in peri-hematoma regions of the ICH-induced rat brain. TNF-${\alpha}$ immuno-labeled cells were coincided with MPO immuno-labeled neutrophils in peri-hematoma regions of the ICH-induced rat brain. Conclusion : These results suggest that SMR plays a protective role against the blood-brain barrier impairment in the ICH through suppression of inflammation in the rat brain tissues.

Keywords

References

  1. Manaenko A, Chen H, Kammer J, Zhang JH, Tang J. Comparison Evans blue injection routes: Intravenous versus intraperitoneal, for measurement of blood-brain barrier in a mice hemorrhage model. J Neurosci Methods. 2011 ; 195(2) : 206-10. https://doi.org/10.1016/j.jneumeth.2010.12.013
  2. Claassen J, Carhuapoma JR, Kreiter KT, Du EY, Connolly ES, Mayer SA. Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome. Stroke. 2002 ; 33 : 1225-32. https://doi.org/10.1161/01.STR.0000015624.29071.1F
  3. Abbott NJ. Inflammatory Mediators and Modulation of Blood-Brain Barrier Permeability. Cell Mol Neurobiol. 2000 ; 20(2) : 131-47. https://doi.org/10.1023/A:1007074420772
  4. Simard JM, Kent TA, Chen M, Tarasov KV, Gerzanich V. Brain oedema in focal ischaemia : molecular pathophysiology and theoretical implications. Lancet Neurol. 2007 ; 6 : 258-68. https://doi.org/10.1016/S1474-4422(07)70055-8
  5. Alvarez-Diaz A, Hilario E, de Cerio FG, Valls-i-Soler A, Alvarez-Diaz FJ. Hypoxic-ischemic injury in the immature brain-key vascular and cellular players. Neonatology. 2007 ; 92 : 227-35. https://doi.org/10.1159/000103741
  6. Moxon-Emre I, Schlichter LC. Neutrophil depletion reduces blood-brain barrier breakdown, axon injury, and inflammation after intracerebral hemorrhage. J Neuropathol Exp Neurol. 2011 ; 70(3) : 218-35. https://doi.org/10.1097/NEN.0b013e31820d94a5
  7. Kim HC. Herbal Pharmacology. Seoul : Jipmundang. 2001 : 332-4.
  8. Herbology department of all-korea oriiental medicine colleges. Herbalogy. Seoul : Youngrimsa. 1995 : 419-20.
  9. Yun HJ, Heo SK, Yun HJ, Park WH, Park SD. Anti-inflammatory effect Salviae Miltiorrhizae Radix. Kor J Herbology. 2007 ; 22(4) : 65-73.
  10. Im NK. Antioxidative and antithrombotic effect of Salvia miltiorrhiza Bunge and it's bioactive components. Keimyung University Graduate School. 2008.
  11. Yang SA, Im NK, Lee IS. Effect of Methanolic Extract from Salviae Miltiorrhiza Bunge on in vitro Antithrombotic and Antioxidative Activities. K J Food Sci Technol. 2007 ; 39 : 83-7.
  12. Fana GW, Gaoa XM, Hong WG, Yan Z, Ju Z, Hua LM, Sua YF, Kanga LY, Zhanga BL. The anti-inflammatory activities of Tanshinone IIA, an active component of TCM, are mediated by estrogen receptor activation and inhibition of iNOS. J Steroid Biochem Mol Biol. 2009 ; 113(3-5) : 275-80. https://doi.org/10.1016/j.jsbmb.2009.01.011
  13. Lee HG, Kim YS. Effects of Salvia Miltriorrhiza Radix on Neuronal Apoptosis following Intracerebral Hemorrhage in Rats. Kor J Herbology. 2012 ; 27(3) : 89-94. https://doi.org/10.6116/kjh.2012.27.3.89
  14. Shim HN, Seong KM, Moon SJ, Lee SH. The Effect of the Salvia miltiorrhiza on Axon Regeneration Following Central Nervous System Injury. J Korean Oriental Med 2008 ; 29(2) : 47-59.
  15. Song JH. Effects of Salviae Miltiorrhizae Radix on Brain Edema and iNOS Expression of ICH-Induced Rats. Kyunghee University East-West Medicine Graduate School. 2010.
  16. Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M. Collagenase induced intracerebral hemorrhage in rats. Stroke. 1990 ; 21 : 801-7. https://doi.org/10.1161/01.STR.21.5.801
  17. Del VJ, Camins A, Pallas M, Vilaplana J, Pelegri C. A new method for determining blood-brain barrier integrity based on intracardiac perfusion of an Evans blue-Hoechst cocktail. J Neurosci Methods. 2008 ; 174(1) : 42-9. https://doi.org/10.1016/j.jneumeth.2008.06.025
  18. Sin MG. Clinical Herbalogy. Seoul : Younlim Publishers. 1989 ; 372-4.
  19. Lee SG, An DK, Sin MG, No SG, Lee YJ, Kim SH. Herbal Clinical application. Seoul : Sungbosa. 1990 ; 269-71.
  20. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001 ; 344 : 1450-60. https://doi.org/10.1056/NEJM200105103441907
  21. Norrving B. Cerebral hemorrhage. Cerebrovascular Disease: Pathophysiology Diagnosis and Management. Malden Mass : Blackwell Science. 1998 : 56.
  22. Fogelholm R, Nuutila M, Vuorela AL. Primary intracerebral haemorrhage in the Jyvaskyla region, central Finland, 1985-89: incidence, case fatality rate, and functional outcome. J Neurol Neurosurg Psychiatry. 1992 ; 55 : 546-52. https://doi.org/10.1136/jnnp.55.7.546
  23. Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Intracerebral hemorrhage versus infarction: stroke severity, risk factors, and prognosis. Ann Neurol. 1995 ; 38 : 45-50. https://doi.org/10.1002/ana.410380110
  24. Lyden PD, Zivin JA. Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence. Cerebrovasc Brain Metab Rev. 1993 ; 5 : 1-16.
  25. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001 ; 344(19) : 1450-60. https://doi.org/10.1056/NEJM200105103441907
  26. Reese TS, Karnovsky MJ. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967 ; 34 : 207-17. https://doi.org/10.1083/jcb.34.1.207
  27. Brown RC, Davis TP. Calcium Modulation of Adherens and Tight Junction Function : A Potential Mechanism for Blood-Brain Barrier Disruption After Stroke. Stroke 2002 ; 33 : 1706-11. https://doi.org/10.1161/01.STR.0000016405.06729.83
  28. Abbruscato TJ, Davis TP. Combination of hypoxia/aglycemia compromises in vitro blood-brain barrier integrity. J Pharmacol Exp Ther. 1999 ; 289 : 668-75.
  29. Banks WA, Jaspan JB, Kastin AJ. Effect of diabetes mellitus on the permeability of the blood-brain barrier to insulin. Peptides. 1997 ; 18 : 1577-84. https://doi.org/10.1016/S0196-9781(97)00238-6
  30. Kalaria RN. The blood-brain barrier and cerebrovascular pathology in Alzheimer's disease. Ann N Y Acad Sci. 1999 ; 893 : 113-25. https://doi.org/10.1111/j.1749-6632.1999.tb07821.x
  31. Huber JD, Witt KA, Hom S, Egleton RD, Mark KS, Davis TP. Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression. Am J Physiol. 2001 ; 280 : H1241-8.
  32. Keep RF, Xiang J, Ennis SR, Andjelkovic A, Hua Y, Xi G, Hoff JT. Blood-brain barrier function in intracerebral hemorrhage. Acta Neurochir Suppl. 2008 ; 105 : 73-7. https://doi.org/10.1007/978-3-211-09469-3_15
  33. Xi G, Keep RF, Hoff JT. Pathophysiology of brain edema formation. Neurosurg Clin N Am. 2002 ; 13 : 371-83. https://doi.org/10.1016/S1042-3680(02)00007-4
  34. Manaenko A, Chen H, Kammer J, Zhang JH, Tang J. Comparison Evans blue injection routes: Intravenous versus intraperitoneal, for measurement of blood-brain barrier in a mice hemorrhage model. J Neurosci Methods. 2011 ; 195(2) : 206-10. https://doi.org/10.1016/j.jneumeth.2010.12.013
  35. Filep JG, El Kebir D. Neutrophil apoptosis: a target for enhancing the resolution of inflammation. J Cell Biochem. 2009 ; 108(5) : 1039-46. https://doi.org/10.1002/jcb.22351
  36. Malle E, Furtmuller PG, Sattler W, Obinger C. Myeloperoxidase: a target for new drug development?. Br J Pharmacol. 2007 ; 152(6) : 838-54. https://doi.org/10.1038/sj.bjp.0707358
  37. Matsubara T, Pararajasegaram G, Wu GS, Rao NA. Retinal microglia differentially express phenotypic markers of antigen-pre-senting cells in vitro. Invest Ophthalmol Vis Sci. 1999 ; 40 : 3186-93.
  38. Arvin B, Neville LF, Barone FC, Feuerstein GZ. The role of inflammation and cytokines in brain injury. Neurosci Biobehav Rev. 1996 ; 20 : 445-52. https://doi.org/10.1016/0149-7634(95)00026-7
  39. Gearing AJ, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, Drummond AH, Galloway WA, Gilbert R, Gordon JL. Processing of tumour necrosis factor-alpha precursor by metalloprot-einases. Nature. 1994 ; 370 : 555-7. https://doi.org/10.1038/370555a0
  40. Bethea JR, Gillespie GY, Chung IY, Benveniste EN. Tumor necrosis factor production and receptor expression by a human malignant glioma cell line, D54-MG. J Neuroimmunol. 1990 ; 30 : 1-13. https://doi.org/10.1016/0165-5728(90)90047-Q