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Thorac Cardiovasc Surg 2005; 53(3): 133-137
DOI: 10.1055/s-2005-837549
Original Cardiovascular

© Georg Thieme Verlag KG Stuttgart · New York

Neuroprotective Effect of 1-Aminocyclopropanecarboxylic Acid in a Rabbit Spinal Ischemia Model

H. Unno1 , T. Jikuya1 , T. Yamamoto1 , Y. Sakakibara1
  • 1Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
Further Information

Publication History

Received August 10, 2004

Publication Date:
30 May 2005 (online)

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Abstract

Background: Postoperative paraplegia remains a serious complication after repair of a thoracoabdominal aortic aneurysm. The release of the excitatory neurotransmitter glutamate might be responsible for ischemic neuronal damage. We investigated the effect of 1-Aminocyclopropanecarboxylic acid (ACPC) on the prevention of paraplegia in a rabbit model of spinal cord ischemia. Methods: The infrarenal abdominal aorta was clamped in eighteen rabbits. Saline (group A), 20 mg/kg of ACPC (group B), or 10 mg/kg of ACPC (group C), was injected into the clamped aorta. The animals were neurologically evaluated by Tarlov's score. The spinal cord was obtained for histopathologic examination, including hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining method. Results: Postoperative complete paraplegia with marked neuronal necrosis appeared in group A animals. Four of the six group C animals showed intact neurological function. Scattered TUNEL positive neurons were seen within areas containing necrotic cells in sections from paraplegic animals in group A. Conclusions: ACPC can prevent spinal cord injury in a rabbit model of spinal cord ischemia.

Key words

Aortic surgery - spinal cord - ischemia - animal model - apoptosis

References

  • 1 Svensson L G, Crawford E S, Hess K R, Coselli J S, Safi H J. Experience with 1509 patients undergoing thoracoabdominal aortic aneurysm.  J Vasc Surg. 1993;  17 357-370
    CrossrefPubMedGoogle Scholar
  • 2 Coselli J S. Thoracoabdominal aortic aneurysms: Experience with 372 patients.  J Card Surg. 1994;  9 638-647
    PubMedGoogle Scholar
  • 3 Grabitz K, Sandmann W, Stühmeier K. et al . The risk of ischemic spinal cord injury in patients undergoing graft replacement for thoracoabdominal aortic aneurysms.  J Vasc Surg. 1996;  23 230-240
    PubMedGoogle Scholar
  • 4 Safi H J, Miller C C, Carr C. et al . Importance of intercostal artery reattachment during thoracoabdominal aortic aneurysm repair.  J Vasc Surg. 1998;  27 58-68
    PubMedGoogle Scholar
  • 5 Svensson L G, Hess K R, Coselli J S, Safi H J. Influence of segmental arteries, extent, and atriofemoral bypass on postoperative paraplegia after thoracoabdominal aortic aneurysm repairs.  J Vasc Surg. 1994;  20 255-262
    CrossrefPubMedGoogle Scholar
  • 6 Mitani A, Kataoka K. Critical levels of extracellular glutamate mediating gerbil hippocampal delayed neuronal death during hypothermia: brain microdialysis study.  Neuroscience. 1991;  42 661-670
    CrossrefPubMedGoogle Scholar
  • 7 Mori A, Ueda T, Nakamichi T. et al . Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo.  Ann Thorac Surg. 1997;  63 1057-1062
    CrossrefPubMedGoogle Scholar
  • 8 Choi D W, Maulucci-Gedde M, Kriegstein A R. Glutamate neurotoxicity in cortical cell culture.  J Neurosci. 1987;  7 357-368
    PubMedGoogle Scholar
  • 9 Follis F, Miller K, Scremin O U, Pett S, Kessler R, Wernly J. NMDA receptor blockade and spinal cord ischemia due to aortic crossclamping in the rat model.  Can J Neurol Sci. 1994;  21 227-232
    PubMedGoogle Scholar
  • 10 Rokkas C K, Helfrich Jr L R, Lobner D C, Choi D W, Kouchoukos N T. Dextrophan inhibits the release of excitatory amino acids during spinal cord ischemia.  Ann Thorac Surg. 1994;  58 312-320
    PubMedGoogle Scholar
  • 11 Marvizon J CG, Lewin A H, Skolnick P. 1-Aminocyclopropane carboxylic acid: A potent and selective ligand for the glycine modulatory site of the N-methyl-D-aspartate receptor complex.  J Neurochem. 1989;  52 992-994
    PubMedGoogle Scholar
  • 12 Fossom L H, Lubitz D KJE, Lin R CS, Skolnick P. Neuroprotective actions of 1-amino-cyclopropanecarboxylic acid (ACPC): A partial agonist at strychynine-insensitive glycine sites.  Neurol Res. 1995;  17 265-269
    PubMedGoogle Scholar
  • 13 Choi D W. Glutamate neurotoxicity and disease of the nervous system.  Neuron. 1988;  1 623-634
    CrossrefPubMedGoogle Scholar
  • 14 Buchan A, Pulsinelli W A. Hypothermia but not N-methyl-D-aspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia.  J Neurosci. 1990;  10 311-316
    PubMedGoogle Scholar
  • 15 DeGirolami U, Zivin J A. Neuropathology of experimental spinal cord ischemia in the rabbit.  J Neuropathol Exp Neurol. 1982;  41 129-149
    PubMedGoogle Scholar
  • 16 Gonzalez-Fajardo J A, Aguirre B, Perez-Burkhardt J L. et al . Epidural regional hypothermia for prevention of paraplegia after aortic occlusion: Experimental evaluation in a rabbit model.  J Vasc Surg. 1996;  23 446-452
    PubMedGoogle Scholar
  • 17 Sureda F X, Viu E, Zapata A. et al . Modulation of NMDA-induced cytosolic calcium levels by ACPC in cultured cerebellar granule cells.  Neuro Report. 1996;  7 1824-1828
    PubMedGoogle Scholar
  • 18 Kerr J F, Wyllie A H, Currie A R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.  Br J Cancer. 1972;  26 239-257
    CrossrefPubMedGoogle Scholar
  • 19 Gavrieli Y, Sherman Y, Ben-Sasson S A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.  J Cell Biol. 1992;  119 493-501
    CrossrefPubMedGoogle Scholar
  • 20 Kato H, Kanellopoulos G K, Matsuo S. et al . Protection of rat spinal cord from ischemia with dextrorphan and cycloheximide: effects on necrosis and apoptosis.  J Thorac Cardiovasc Surg. 1997;  114 609-618
    PubMedGoogle Scholar

MD, PhD Yuzuru Sakakibara

Department of Surgery, Institute of Clinical Medicine, University of Tsukuba

1-1-1 Tennodai

Tsukuba-City, Ibaraki 305-8575

Japan

Phone: + 81298533210

Fax: 81 2 98 53 30 39

Email: kensan@md.tsukuba.ac.jp

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