Journal of Korean Neurosurgical Society

  • 제50권6호
  • /
  • Pages.481-485
  • /
  • 2011
  • /
  • 2005-3711(pISSN)
  • /
  • 1598-7876(eISSN)
대한신경외과학회 (The Korean Neurosurgical Society)
권호 표지
DOI QR코드

DOI QR Code

Serial Expression of Hypoxia Inducible Factor-$1{\alpha}$ and Neuronal Apoptosis in Hippocampus of Rats with Chronic Ischemic Brain

  • Yu, Chi-Ho (Department of Veterinary Pathobiology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University) ;
  • Moon, Chang-Taek (Department of Neurosurgery, Konkuk University Medical Center) ;
  • Sur, Jung-Hyang (Department of Veterinary Pathobiology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University) ;
  • Chun, Young-Il (Department of Neurosurgery, Konkuk University Medical Center) ;
  • Choi, Won-Ho (Department of Neurosurgery, Konkuk University Medical Center) ;
  • Yhee, Ji-Young (Department of Veterinary Pathobiology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University)
  • 투고 : 2011.08.22
  • 심사 : 2011.12.19
  • 발행 : 2011.12.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective : The purpose of this study is to investigate serial changes of hypoxia-inducible factor $1{\alpha}$ (HIF-$1{\alpha}$), as a key regulator of hypoxic ischemia, and apoptosis of hippocampus induced by bilateral carotid arteries occlusion (BCAO) in rats. Methods : Adult male Wistar rats were subjected to the permanent BCAO. The time points studied were 1, 2, 4, 8, and 12 weeks after occlusions, with n=6 animals subjected to BCAO, and n=2 to sham operation at each time point, and brains were fixed by intracardiac perfusion fixation with 4% neutral-buffered praraformaldehyde for brain section preparation. Immunohistochemistry (IHC), western blot and terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate HIF-$1{\alpha}$ expression and apoptosis. Results : In IHC and western blot, HIF-$1{\alpha}$ levels were found to reach the peak at the 2nd week in the hippocampus, while apoptotic neurons, in TUNEL assay, were maximal at the 4th week in the hippocampus, especially in the cornu ammonis 1 (CA1) region. HIF-$1{\alpha}$ levels and apoptosis were found to fluctuate during the time course. Conclusion : This study showed that BCAO induces acute ischemic responses for about 4 weeks then chronic ischemia in the hippocampus. These in vivo data are the first to show the temporal sequence of apoptosis and HIF-$1{\alpha}$ expression.

키워드

참고문헌

  1. Bennett SA, Tenniswood M, Chen JH, Davidson CM, Keyes MT, Fortin T, Pappas BA : Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment. Neuroreport 9 : 161-166, 1998 https://doi.org/10.1097/00001756-199801050-00033
  2. Bergeron M, Yu AY, Solway KE, Semenza GL, Sharp FR : Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eur J Neurosci 11 : 4159-4170, 1999 https://doi.org/10.1046/j.1460-9568.1999.00845.x
  3. Chavez JC, LaManna JC : Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia : potential role of insulin-like growth factor-1. J Neurosci 22 : 8922-8931, 2002
  4. Choki JI, Yamaguchi T, Takeya Y, Morotomi Y, Omae T : Effect of carotid artery ligation on regional cerebral blood flow in normotensive and spontaneously hypertensive rats. Stroke 8 : 374-379, 1977 https://doi.org/10.1161/01.STR.8.3.374
  5. Choy M, Ganesan V, Thomas DL, Thornton JS, Proctor E, King MD, et al. : The chronic vascular and haemodynamic response after permanent bilateral common carotid occlusion in newborn and adult rats. J Cereb Blood Flow Metab 26 : 1066-1075, 2006
  6. Clendenon NR, Allen N, Komatsu T, Liss L, Gordon WA, Heimberger K : Biochemical alterations in the anoxic-ischemic lesion of rat brain. Arch Neurol 25 : 432-448, 1971 https://doi.org/10.1001/archneur.1971.00490050066006
  7. de la Torre JC, Fortin T, Park GA, Butler KS, Kozlowski P, Pappas BA, et al. : Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats. Brain Res 582 : 186-195, 1992 https://doi.org/10.1016/0006-8993(92)90132-S
  8. de la Torre JC, Fortin T, Park GA, Pappas BA, Richard MT : Brain blood flow restoration 'rescues' chronically damaged rat CA1 neurons. Brain Res 623 : 6-15, 1993 https://doi.org/10.1016/0006-8993(93)90003-6
  9. Farkas E, Luiten PG : Cerebral microvascular pathology in aging and Alzheimer's disease. Prog Neurobiol 64 : 575-611, 2001 https://doi.org/10.1016/S0301-0082(00)00068-X
  10. Farkas E, Luiten PG, Bari F : Permanent, bilateral common carotid artery occlusion in the rat : a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 54 : 162-180, 2007 https://doi.org/10.1016/j.brainresrev.2007.01.003
  11. Garcia JH : Experimental ischemic stroke : a review. Stroke 15 : 5-14, 1984 https://doi.org/10.1161/01.STR.15.1.5
  12. Garcia JH, Mitchem HL, Briggs L, Morawetz R, Hudetz AG, Hazelrig JB, et al. : Transient focal ischemia in subhuman primates. Neuronal injury as a function of local cerebral blood flow. J Neuropathol Exp Neurol 42 : 44-60, 1983 https://doi.org/10.1097/00005072-198301000-00004
  13. Goda N, Ryan HE, Khadivi B, McNulty W, Rickert RC, Johnson RS : Hypoxia-inducible factor 1alpha is essential for cell cycle arrest during hypoxia. Mol Cell Biol 23 : 359-369, 2003 https://doi.org/10.1128/MCB.23.1.359-369.2003
  14. Greijer AE, van der Wall E : The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol 57 : 1009-1014, 2004 https://doi.org/10.1136/jcp.2003.015032
  15. He Z, Ibayashi S, Sugimori H, Fujii K, Sadoshima S, Fujishima M : Age-related ischemia in the brain following bilateral carotid artery occlusion--collateral blood flow and brain metabolism. Neurochem Res 22 : 37-42, 1977
  16. Kim HS, Lee HJ, Yeu IS, Yi JS, Yang JH, Lee IW : The neovascularization effect of bone marrow stromal cells in temporal muscle after encephalomyosynangiosis in chronic cerebral ischemic rats. J Korean Neurosurg Soc 44 : 249-255, 2008 https://doi.org/10.3340/jkns.2008.44.4.249
  17. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, et al. : The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399 : 271-275, 1999 https://doi.org/10.1038/20459
  18. Michiels C : Physiological and pathological responses to hypoxia. Am J Pathol 164 : 1875-1882, 2004 https://doi.org/10.1016/S0002-9440(10)63747-9
  19. Ni JW, Matsumoto K, Li HB, Murakami Y, Watanabe H : Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in rat. Brain Res 673 : 290-296, 1995 https://doi.org/10.1016/0006-8993(94)01436-L
  20. Ohta H, Nishikawa H, Kimura H, Anayama H, Miyamoto M : Chronic cerebral hypoperfusion by permanent internal carotid ligation produces learning impairment without brain damage in rats. Neuroscience 79 : 1039-1050, 1997 https://doi.org/10.1016/S0306-4522(97)00037-7
  21. Ohtaki H, Fujimoto T, Sato T, Kishimoto K, Fujimoto M, Moriya M, et al. : Progressive expression of vascular endothelial growth factor (VEGF) and angiogenesis after chronic ischemic hypoperfusion in rat. Acta Neurochir Suppl 96 : 283-287, 2006
  22. Oldendorf WH : Trophic changes in the arteries at the base of the rat brain in response to bilateral common carotid ligation. J Neuropathol Exp Neurol 48 : 534-547, 1989 https://doi.org/10.1097/00005072-198909000-00004
  23. Otori T, Katsumata T, Muramatsu H, Kashiwagi F, Katayama Y, Terashi A : Long-term measurement of cerebral blood flow and metabolism in a rat chronic hypoperfusion model. Clin Exp Pharmacol Physiol 30 : 266-272, 2003 https://doi.org/10.1046/j.1440-1681.2003.03825.x
  24. Pappas BA, de la Torre JC, Davidson CM, Keyes MT, Fortin T : Chronic reduction of cerebral blood flow in the adult rat : late-emerging CA1 cell loss and memory dysfunction. Brain Res 708 : 50-58, 1996 https://doi.org/10.1016/0006-8993(95)01267-2
  25. Salceda S, Caro J : Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem 272 : 22642-22647, 1997 https://doi.org/10.1074/jbc.272.36.22642
  26. Salford LG, Plum F, Siesjö BK : Graded hypoxia-oligemia in rat brain. I. Biochemical alterations and their implications. Arch Neurol 29 : 227-233, 1973 https://doi.org/10.1001/archneur.1973.00490280039005
  27. Schmidt-Kastner R, Aguirre-Chen C, Saul I, Yick L, Hamasaki D, Busto R, et al. : Astrocytes react to oligemia in the forebrain induced by chronic bilateral common carotid artery occlusion in rats. Brain Res 1052 : 28-39, 2005 https://doi.org/10.1016/j.brainres.2005.06.018
  28. Semenza GL : HIF-1 : mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 88 : 1474-1480, 2000
  29. Semenza GL : Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE : cm8, 2007
  30. Tomimoto H, Ihara M, Wakita H, Ohtani R, Lin JX, Akiguchi I, et al. : Chronic cerebral hypoperfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat. Acta Neuropathol 106 : 527-534, 2003 https://doi.org/10.1007/s00401-003-0749-3
  31. Ulrich PT, Kroppenstedt S, Heimann A, Kempski O : Laser-Doppler scanning of local cerebral blood flow and reserve capacity and testing of motor and memory functions in a chronic 2-vessel occlusion model in rats. Stroke 29 : 2412-2420, 1998 https://doi.org/10.1161/01.STR.29.11.2412
  32. Wang GL, Jiang BH, Rue EA, Semenza GL : Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 92 : 5510-5514, 1995 https://doi.org/10.1073/pnas.92.12.5510
  33. Wenger RH : Cellular adaptation to hypoxia : O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. FASEB J 16 : 1151-1162, 2002

피인용 문헌

  1. Catuaba (Trichilia catigua) Prevents Against Oxidative Damage Induced by In Vitro Ischemia-Reperfusion in Rat Hippocampal Slices vol.37, pp.12, 2011, https://doi.org/10.1007/s11064-012-0876-0
  2. Hypoxia Markers are Expressed in Interneurons Exposed to Recurrent Seizures vol.15, pp.1, 2011, https://doi.org/10.1007/s12017-012-8203-0
  3. Learning and survival memory undergoing a permanent bilateral carotid ligation in rats vol.28, pp.2, 2011, https://doi.org/10.1590/s0102-86502013000200003
  4. Apoptotic mechanisms after repeated noise trauma in the mouse medial geniculate body and primary auditory cortex vol.235, pp.12, 2017, https://doi.org/10.1007/s00221-017-5091-4
  5. Time course of cell death due to acoustic overstimulation in the mouse medial geniculate body and primary auditory cortex vol.19, pp.88, 2011, https://doi.org/10.4103/nah.nah_10_17