Annals of Occupational and Environmental Medicine

The Korean Society of Occupational & Environmental Medicine (대한직업환경의학회)
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The Brain Pathology on Recovery of Brain MRI after Manganese Administration in Rats

흰쥐에서 망간 투여 후 뇌자기공명영상에서 고신호 강도 회복시 뇌 병리학적 소견

  • Jung, Ji-Hyeon (Department of Occupational & Environmental Medicine, College of Medicine, Dong-A University) ;
  • Kim, Jung-Il (Department of Occupational & Environmental Medicine, College of Medicine, Dong-A University) ;
  • Kim, Se-Young (Department of Occupational & Environmental Medicine, College of Medicine, Dong-A University) ;
  • Jung, Min-Ho (Department of Microbiology, College of Medicine, Dong-A University) ;
  • Choi, Soon-Sub (Department of Radiology, College of Medicine, Dong-A University) ;
  • Kim, Soo-Jin (Department of Pathology, College of Medicine, Dong-A University) ;
  • Park, Young-Jin (Department of Family Medicine, College of Medicine, Dong-A University) ;
  • Jung, Kap-Yeol (Department of Occupational & Environmental Medicine, College of Medicine, Dong-A University)
  • 정지현 (동아대학교 의과대학 산업의학교실) ;
  • 김정일 (동아대학교 의과대학 산업의학교실) ;
  • 김세영 (동아대학교 의과대학 산업의학교실) ;
  • 정민호 (동아대학교 의과대학 미생물학교실) ;
  • 최순섭 (동아대학교 의과대학 영상의학교실) ;
  • 김수진 (동아대학교 의과대학 병리학교실) ;
  • 박영진 (동아대학교 의과대학 가정의학교실) ;
  • 정갑열 (동아대학교 의과대학 산업의학교실)
  • Received : 2010.09.29
  • Accepted : 2010.12.17
  • Published : 2010.12.31
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Abstract

Objectives: This study was carried out to investigate the effect on manganese on the brain of Sprague-Dawley rats, with particular focus on changes to anatomical pathology when brain MRI was recovered after manganese administration. Methods: There were 15 rats divided into 3 groups of 5 based on dose of manganese: control group, low dose group (10 mg/kg), and high dose group (40 mg/kg). Each dosing group received an injection of normal saline and manganese via the tail vein once a week for 4 weeks. And then, the rats were observed for 12 weeks after stopping manganese administration. Next, each rat underwent a brain MRI and then each was sacrificed. After the rats were killed, the concentrations of blood manganese were measured, and pathologic examinations of the brain were performed. Results: The signal intensity of basal ganglia on T1-weighted imaging of brain MRI did not differ between dosing groups. However, the ratio of neuron/glial cell in the basal ganglia was decreased in the low- and high-dose groups compared to the control group. Conclusions: This study showed that the damage of neuron in basal ganglia might be permanent after signal intensity of basal ganglia on T1-weighted imaging of brain MRI was recovered.

목적: 본 연구는 망간에 노출시킨 실험동물 모델을 이용하여 흰쥐에서 용량에 따라 망간 투여 후 회복시의 뇌자기공명영상과 병리조직학적 변화를 확인하고, 뇌 자기공명영상에서 고신호강도가 사라진 후에도 뇌조직의 손상이 지속되는지 여부를 확인하고자 하였다. 방법: 흰쥐를 15를 5마리씩 대조군, 저용량군과 대조군의 세 군으로 나누고 각각의 군에 생리식염수, 망간 10 mg/kg, 40 mg/kg을 1주에 1회 4주간 투여하였다. 12주 동안의 회복기간을 거친 후 뇌 자기공명영상을 촬영하고 희생시켜 부검을 통해 혈액과 뇌를 채취하였다. 채취한 혈액의 망간 농도를 분석하였고, 뇌 반구는 기저핵이 포함된 조직절편을 염색하여 병리조직학적 변화를 관찰하였다. 결과: 뇌 자기공명영상에서는 기존의 기저핵 고신호강도는 관찰되지 않았으나, 실험군은 대조군에 비해 뇌 기저핵에서 교세포 수에 대한 신경세포 수의 비가 감소되어 있었다. 결론: 뇌 자기공명영상에서 고신호강도가 사라지고 난후에도 뇌의 병리조직학적 이상소견은 여전히 존재할 수 있는 점을 확인할 수 있었다.

Keywords

References

  1. Park CY, Roh YM, Koo JW, Lee SH. Manganese exposure in ore crushing. Korean J Occup Environ Med 1991;1(3):111-8.(Korean)
  2. Kim JY, Lim HS, Cheong HK, Paik NW. A study on the manganese exposure and health hazards among manganese manufacturing workers. Korean J Occup Environ Med 1994;6(1):98-112.(Korean)
  3. Kim Y, Kim JW, Ito K, Lim HS, Cheong HK, Kim JY, Shun YC, Kim KS, Moon Y. Idiopathic parkinsonism with superimposed manganese exposure: utility of positron emission tomograpy. Neurotoxicology 1999;20(2-3):249-52.
  4. Tanaka S, Lieben J. Manganese poisoning and exposure in Peensylvania. Arch Environ health 1969;19:674-84. https://doi.org/10.1080/00039896.1969.10666909
  5. Mena I, Marin O, Fuenzalida S, Cotzias GC. Chronic manganese poisoning. Clinical picture and manganese turnover. Neurology 1967;17:128-36. https://doi.org/10.1212/WNL.17.2.128
  6. Smith LT, Ruhf RC, Whiteman NE, Dugan T. Clinical manganism and exposure to manganese in the production and processing of ferromanganese alloy. J Occup Med 1973;15:101-9.
  7. Yamada M, Ohno S, Okayasu I, Okeda R, Hatakeyama S, Watanabe H, Ushio K, Tsukagoshi H. Chronic manganesepoisoning: a neuropathological study with determination of manganese distribution in the brain. Acta Neuropathol 1986;70:273-8. https://doi.org/10.1007/BF00686083
  8. Newland MC, Ceckler T, Kordower J, Weiss B. Visualizing manganese in the primate basal ganglia with magnetic resonance imaging. Exp Neurol 1989;106:251-8. https://doi.org/10.1016/0014-4886(89)90157-X
  9. Dorman DC, Struve MF, Wong BA, Dye JA, Robertson ID. Correlation of brain magnetic resonance imaging changes with pallidal manganese concentrations in rhesus monkeys following subchronic manganese inhalation. Toxicol Sci 2006;92:219-27. https://doi.org/10.1093/toxsci/kfj209
  10. Park NH, Park JK, Choi Y, Yoo C-I, Lee CR, Lee H, Kim HK, Kim S-R, Jung TH, Park J, Yoon CS, Kim Y. Whole blood manganese correlates with high signal intensities on T1-weighted MRI in patients with liver cirrhosis. Neurotoxicology 2003;24(6):909-15. https://doi.org/10.1016/S0161-813X(03)00111-6
  11. Eriksson H, Tedroff J, Thuomas KA, Aquilonius SM, Hartvig P, Fasth KJ, Bjurling P, Langstrom B, Hedstrom KG, Heilbronn E. Manganese induced brain lesion in Macaca fiscicularis as revealed by positron emission tomography and magnetic resonance imaging. Arch Toxicol 1992;66:406-7.
  12. Sung JH, Kim CY, Yang SO, Khang HS, Cheong HK, Lee JS, Song CW, Park JD, Han JH, Chung YH, Choi BS, Kwon IH, Cho MH, Yu IJ. Changes in blood manganese concentration and MRI T1 relaxation time during 180 days of stainless steel welding-fume exposure in cynomolgus monkeys. Inhal Toxicol 2007;19:47-55. https://doi.org/10.1080/08958370600985834
  13. Nelson K, Golnick J, Korn T, Angle C. Manganese encephalopathy: utility of early magnetic resonance imaging. Br J Ind Med 1993;50:510-3.
  14. Mirowitz SA, Westrich TJ. Basal ganglial signal intensity alteration: reversal after discontinuation of parnteral manganese administration. Radiology 1992;185:535-6.
  15. Kim SH, Chang KH, Chi JG, Cheong HK, Kim JY, Kim YM, Han MH. Sequential change of MR signal intensity of the brain after manganese administration in rabbits: Correlation with manganese concentration and histopathologic findings invest Radiol 1999;34:383-93. https://doi.org/10.1097/00004424-199906000-00001
  16. Shinotoh H, Snow BJ, Hewitt KA, Hewitt KA, Pate BD, Doudet D, Nugent R, Perl DP, Olanow W, Calne DB. MRI and PET studies of manganese-intoxicated monkeys. Neurology 1995;45:1199-204. https://doi.org/10.1212/WNL.45.6.1199
  17. Lee JM, Kim JI, Kim YK, Jung MH, Choi SS, Kim DC, Jung KY. The change of brain MRI and pathology according to the administered dose of manganese in rats. Korean J Occup Environ Med 2009;21(2):184-91. (Korean)
  18. Hong YS, Lim MA, Lee YH, Cheong HK, Kim JY, Lim HS, Lee JJ, Sa KJ, Kim JY. Three cases of high signal intensity by brain magnetic resonance imaging in $CO_2$ arc welders. Korean J Occup Environ Med 1998;10(2):290-8. (Korean)
  19. Jang TJ, Kim JR, Lee JI, Kim DH, Kim KK, Kim JY, Cheong HK. Manganese intoxication in the Rat: a neuropathologic study and distribution of manganese in rat brain. Korean Journal of Pathology 1999;33:662-74. (Korean)