The Time Evolution of Cerebral Apoptosis in the Permanent Middle Cerebral Artery Occlusion Model in Rats

  • Shin, Cheol-Sik (Department of Neurosurgery, College of Medicine, Yeungnam University) ;
  • Choi, Byung-Yon (Department of Neurosurgery, College of Medicine, Yeungnam University) ;
  • Jung, Eul-Soo (Department of Neurosurgery, Bo-Gang Hospita) ;
  • Kim, Sang-Woo (Department of Neurosurgery, College of Medicine, Yeungnam University) ;
  • Chang, Chul-Hoon (Department of Neurosurgery, College of Medicine, Yeungnam University) ;
  • Cho, Soo-Ho (Department of Neurosurgery, College of Medicine, Yeungnam University)
  • Published : 2005.01.31

Abstract

Objective: The purpose of this study is to determine the time evolution and distribution of cerebral apoptosis using the middle cerebral artery occlusion model in rats. Methods: A total of twenty four male rats - with 2, 3, 4, 6, 8, 12, 24 and 48 hours of middle cerebral artery occlusion respectively - were studied. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling(TUNEL) method was used for the observation of the apoptotic cells. The apoptotic ratio was calculated and the distribution of apoptosis was inspected in the pyriform cortex, basal ganglia and middle cerebral artery territory cortex. The rats were divided into three groups(Group I : $2{\sim}4$ hours of occlusion, Group II : $6{\sim}$12 hours of occlusion, Group III : $24{\sim}48$ hours of occlusion). Results: In this study, the proportion of apoptosis increased with the duration of middle cerebral artery occlusion and reached a maximum after about 12 hours of middle cerebral artery occlusion. The mean values of the apoptotic ratio were $30.7{\pm}11.3%$ in group I, $60.8{\pm}2.6%$ in group II and $48.7{\pm}0.7%$ in group III. The distribution of apoptosis differed in the pyriform cortex, basal ganglia and middle cerebral artery territory cortex according to the duration of time of the middle cerebral artery occlusion. Conclusion: In the middle cerebral artery occlusion model of the rats, apoptosis is found to increase according to the occlusion time, reaching a peak after 6 hours, and the distribution of apoptosis changed from the pyriform cortex to the basal ganglia and middle cerebral artery territory cortex.

Keywords

References

  1. Arends MJ, Wyllie AH : Apotosis : mechanisms and roles in pathology. Int Rev Exp Pathol 32 : 223-254, 1991
  2. Buja LM, Eigenbrodt ML, Eigenbrodt EH : Apoptosis and necrosis ; Basic types and mechanisms of cell death. Arch Pathol Lab Med 117 : 1208-1214, 1993
  3. Chin DK, Kim YS, Yoon DH, Joo JY, Lee KH, Seong JK : Cell death in acute spinal cord injury. J Korean Neurosurg Soc 28 : 1755-1764, 1999
  4. Chopp M, Li Y : Apoptosis in focal cerebral ischemia. Acta Neurochir 66 : 21-26, 1996
  5. Cohen JJ : Programmed cell death in the immune system. Adv Immunol 50 : 55-85, 1991 https://doi.org/10.1016/S0065-2776(08)60822-6
  6. Farber JL : Biology of disease; membrane injury and calcium homeostasis in the pathogenesis of coagulative necrosis. Lab Invest 47 : 114-123, 1982
  7. Garvrieli Y, Sherman Y, Sasson SAB : Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119 : 493-501, 1992 https://doi.org/10.1083/jcb.119.3.493
  8. Hockenbery DM, Oltvai ZN, Yin X-M, Milliman CL, Korsmeyer SJ : Bcl- 2 functions in an antioxidant pathway to prevent apoptosis. Cell 75 : 241- 251, 1993 https://doi.org/10.1016/0092-8674(93)80066-N
  9. Hockenbery DM : Defining apoptosis. Am J Pathol 146 : 16-19, 1995
  10. Kerr JFR, Wyllie AH, Currie AR : Apoptosis ; a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26 : 239-257, 1972 https://doi.org/10.1038/bjc.1972.33
  11. Kim BR, Chung YG, Kim HK, Kim CY, Park SH, Lee IW, et al : Evaluation of apoptosis in the normal rat brain after intraoperative irradiation. J Korean Neurosurg Soc 28 : 1089-1099, 1999
  12. Kim MS, Kim TY, Park RK : Brain tumor and apoptosis. J Korean Brain Tumor Soc 1 : 7-15, 2002
  13. Lee SH, Kim M, Kim YA, Kim YJ, Chi JG, Roh JK, et al : Ischemic intensity influences the distribution of delayed infarction and apoptotic cell death following transient focal cerebral ischemia in rats. Brain Res 956 : 14-23, 2002 https://doi.org/10.1016/S0006-8993(02)03197-9
  14. Levine B, Huang Q, Isaacs JT, Reed JC, Griffin DE, Hardwick JM : Conversion of lytic to persistent alphavirus infection by the bcl-2 celluar oncogene. Nature 361 : 739-742, 1993 https://doi.org/10.1038/361739a0
  15. Li Y, Chopp M, Jiang N, Yao F, Zaloga C : Induction of DNA fragmentation after 10 to 120 mimnutes of focal cerebral ischemia in rats. Stroke 26 : 1252- 1258, 1995 https://doi.org/10.1161/01.STR.26.7.1252
  16. Li Y, Chopp M, Jiang N, Yao F, Zaloga C : Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 15 : 389-397, 1995 https://doi.org/10.1038/jcbfm.1995.49
  17. Li Y, Chopp M, Powers C, Jiang N : Apoptosis and protein expression after focal cerebral ischemia in rat. Brain Res 765 : 301-312, 1997 https://doi.org/10.1016/S0006-8993(97)00524-6
  18. Li Y, Powers C, Jiang N, Chopp M : Intact, injured, necrotic and apoptotic cells after focal cerebral ischemia in the rat. J Neurol Sci 156 : 119-132, 1998 https://doi.org/10.1016/S0022-510X(98)00036-7
  19. Li Y, Sharov VG, Jiang N, Zaloga C, Sabbah NH, Chopp M : Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 146 : 1045-1051, 1995
  20. Linnik MD, Miller JA, Cavallo JS, Spinkle-Cavallo J, Mason PJ, Thompson FY, et al : Apoptotic DNA fragmentation in the rat cerabral cortex induced by permanent middle cerebral artery occlusion. Mol Brain Res 32 : 116-124, 1995 https://doi.org/10.1016/0169-328X(95)00069-5
  21. Linnik MD, Zobrist RH, Hatfield MD : Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke 24 : 2002- 2009, 1993 https://doi.org/10.1161/01.STR.24.12.2002
  22. Magnus T, Chan A, Grauer O, Toyka KV, Gold R : Microglial phagocytosis of apoptotic inflammatory T cell leads to down-regulation of microglial immune activation. J Immunol 167 : 5004-5010, 2001 https://doi.org/10.4049/jimmunol.167.9.5004
  23. Majno G, Joris I : Apoptosis, oncosis and necrosis. Am J Pathol 146 : 3-15, 1995
  24. Nagasawa H, Kogure K : Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. Stroke 20 : 1037-1043, 1989 https://doi.org/10.1161/01.STR.20.8.1037
  25. Pulera MR, Adams LM, Liu H, Santos DG, Nishimura RN, Yang F, et al : Apoptosis in a neonatal rat model of cerebral hypoxia-ischemia. Stroke 29 : 2622-2630, 1998 https://doi.org/10.1161/01.STR.29.12.2622
  26. Rink A, Fung KM, Trojanowski JQ, Lee VMY, Neugebauer E, McIntosh TK : Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am J Pathol 147 : 1575-1583, 1995
  27. Rubino GJ, Young W : Ischemic cortical lesions after permanent occlusion of individual middle cerebral artery branches in rats. Stroke 19 : 870-877, 1988 https://doi.org/10.1161/01.STR.19.7.870
  28. Searle J, Kerr JFR, Bishop CJ : Necrosis and apoptosis; distinct modes of cell death with fundamentally different significance. Pathol Annu 17 : 229-259, 1982
  29. Thompson CB : Apoptosis in the pathogenesis and treatment of disease. Science 267 : 1456-1462, 1995 https://doi.org/10.1126/science.7878464
  30. Tominaga T, Kure S, Narisawa K, Yoshimoto T : Endonuclease activation following focal ischmic injury in the rat brain. Brain Res 608 : 21-26, 1993 https://doi.org/10.1016/0006-8993(93)90768-I
  31. Wahl F, Allix M, Plotkine M, Boulu RG : Neurological and behavioral outcomes of focal cerebral ischemia in rats. Stroke 23 : 267-272, 1992 https://doi.org/10.1161/01.STR.23.2.267
  32. Yamada A, Isono M, Hori S, Shimomura T, Nakano T : Temporal and spatial profile of apoptotic cells after focal cerebral ischemia in rats. Neurol Med Chir 39 : 575-583, 1999 https://doi.org/10.2176/nmc.39.575
  33. Yao H, Takasawa R, Fukuda K, Shiokawa D, Akiyoshi FS, Ibayashi S, et al : DNA fragmentation in ischemic core and penumbra in focal cerebral ischemia in rats. Mol Brain Res 91 : 112-118, 2001 https://doi.org/10.1016/S0169-328X(01)00135-8
  34. Yip PK, He YY, Hsu CY, Grag N, Marangos P, Hogan EL : Effect of plasma glucose on infact size in focal cerebral ischemia-reperfusion. Neurology 41 : 899-905, 1991 https://doi.org/10.1212/WNL.41.6.899