Skip to main content
Top
Published in: Annals of Vascular Surgery 2/2006

01-03-2006

Effects of Cyclosporin A on Neurological Outcome and Serum Biomarkers in the Same Setting of Spinal Cord Ischemia Model

Authors: Erdem A. Ozkısacık, MD, Berent Discigil, MD, Mehmet Boga, MD, Ugur Gurcun, MD, Muharrem I. Badak, MD, Tunay Kurtoglu, MD, Cigdem Yenısey, MD, Emel Dıkıcıoglu, MD

Published in: Annals of Vascular Surgery | Issue 2/2006

Login to get access

Abstract

Spinal cord ischemic injury is one of the feared complications during aortic cross-clamping. The aim of this study was to investigate whether cyclosporin A (CsA) has a protective effect on spinal cord during ischemia in a rabbit model. A total of 22 New Zealand white rabbits were studied in three groups. One of the groups served as a sham group (n = 7), in which only laparatomy was performed and closed. One group served as a control group (n = 7), in which rabbits had their abdominal aortas cross-clamped for 40 min following median laparatomy. The last group was the CsA group (n = 8), in which rabbits underwent the same procedure as the control group as well as CsA infusion at 20 mg/(kg · hr) over 60 min starting with aortic cross-clamping and continuing in the first 20 min of reperfusion. Neurological outcome of rabbits was evaluated according to Johnson’s scale at postoperative hours 24 and 48 in all groups, and then they were killed. Their spinal cords were harvested, and segments corresponding to L4-L6 were prepared for pathological examination. Serum neuron-specific enolase (NSE) and nitric oxide (NO) levels were measured prior to and following aortic occlusion, and comparisons were made. Physiological data were similar in all groups. Rabbits in the sham group did not have any neurological deficit. However, all rabbits in the control group showed severe neurological deficits, including total paraplegia in five. According to Johnson’s scale, neurological status of the rabbits at postoperative hour 48 was better in the CsA group compared to controls (p < 0.01). Pathological examination of spinal cord specimens revealed a higher viability index in the CsA group compared to controls (p < 0.01). Serum NSE and NO levels were lower in CsA-treated animals compared to controls. Our results demonstrate that CsA, when administered during ischemia and in the early period of reperfusion, may reduce neuronal damage in the spinal cord in a rabbit model of transient spinal cord ischemia.
Literature
1.
go back to reference Svensson LG, Crawford ES, Hess KR, et al. Experience with 1509 patients undergoing thoracoabdominal aortic operations. J Vasc Surg 1993;17:357–370PubMedCrossRef Svensson LG, Crawford ES, Hess KR, et al. Experience with 1509 patients undergoing thoracoabdominal aortic operations. J Vasc Surg 1993;17:357–370PubMedCrossRef
2.
go back to reference Gharagozloo F, Larson J, Dausmann MJ, et al. Spinal cord protection during surgical procedures on the descending thoracic and thoracoabdominal aorta: review of current techniques. Chest 1996;109:799–809PubMedCrossRef Gharagozloo F, Larson J, Dausmann MJ, et al. Spinal cord protection during surgical procedures on the descending thoracic and thoracoabdominal aorta: review of current techniques. Chest 1996;109:799–809PubMedCrossRef
3.
go back to reference Qayumi AK, Janusz MT, Jamieson WR, et al. Pharmacologic interventions for prevention of spinal cord injury caused by aortic crossclamping. J Thorac Cardiovasc Surg 1992;104:256–261PubMed Qayumi AK, Janusz MT, Jamieson WR, et al. Pharmacologic interventions for prevention of spinal cord injury caused by aortic crossclamping. J Thorac Cardiovasc Surg 1992;104:256–261PubMed
4.
go back to reference Wan IY, Angelini GD, Bryan AJ, et al. Prevention of spinal cord ischaemia during descending thoracic and thoracoabdominal aortic surgery. Eur J Cardiothorac Surg 2001;19:203–213PubMedCrossRef Wan IY, Angelini GD, Bryan AJ, et al. Prevention of spinal cord ischaemia during descending thoracic and thoracoabdominal aortic surgery. Eur J Cardiothorac Surg 2001;19:203–213PubMedCrossRef
5.
go back to reference Atzeni F, Sarzi-Puttini P, Capsoni F, et al. Successful treatment of pure red cell aplasia in systemic lupus erythematosus with cyclosporin A. Clin Exp Rheumatol 2003;21:759–762PubMed Atzeni F, Sarzi-Puttini P, Capsoni F, et al. Successful treatment of pure red cell aplasia in systemic lupus erythematosus with cyclosporin A. Clin Exp Rheumatol 2003;21:759–762PubMed
6.
go back to reference Morris PJ. Cyclosporine, FK-506 and other drugs in organ transplantation. Curr Opin Immunol 1991;3:748–751PubMedCrossRef Morris PJ. Cyclosporine, FK-506 and other drugs in organ transplantation. Curr Opin Immunol 1991;3:748–751PubMedCrossRef
7.
8.
go back to reference Kaminska B, Gaweda-Walerych K, Zawadzka M. Molecular mechanisms of neuroprotective action of immunosuppressants - facts and hypotheses. J Cell Mol Med 2004;8:45–58PubMedCrossRef Kaminska B, Gaweda-Walerych K, Zawadzka M. Molecular mechanisms of neuroprotective action of immunosuppressants - facts and hypotheses. J Cell Mol Med 2004;8:45–58PubMedCrossRef
9.
go back to reference Navarro-Gonzalvez JA, Garcia-Benayas C, Arenas J. Semiautomated measurement of nitrate in biological fluids. Clin Chem 1998;44:679–681PubMed Navarro-Gonzalvez JA, Garcia-Benayas C, Arenas J. Semiautomated measurement of nitrate in biological fluids. Clin Chem 1998;44:679–681PubMed
10.
go back to reference Johnson SH, Kraimer JM, Graeber GM. Effects of flunarizine on neurological recovery and spinal cord blood flow in experimental spinal cord ischemia in rabbits. Stroke 1993;24:1547–1553PubMed Johnson SH, Kraimer JM, Graeber GM. Effects of flunarizine on neurological recovery and spinal cord blood flow in experimental spinal cord ischemia in rabbits. Stroke 1993;24:1547–1553PubMed
11.
go back to reference Almeida A, Delgado-Esteban M, Bolanos JP, et al. Oxygen and glucose deprivation induces mitochondrial dysfunction and oxidative stress in neurones but not in astrocytes in primary culture. J Neurochem 2002;81:207–217PubMedCrossRef Almeida A, Delgado-Esteban M, Bolanos JP, et al. Oxygen and glucose deprivation induces mitochondrial dysfunction and oxidative stress in neurones but not in astrocytes in primary culture. J Neurochem 2002;81:207–217PubMedCrossRef
12.
go back to reference Hansson MJ, Persson T, Friberg H, et al. Powerful cyclosporin inhibition of calcium-induced permeability transition in brain mitochondria. Brain Res 2003;960:99–111PubMedCrossRef Hansson MJ, Persson T, Friberg H, et al. Powerful cyclosporin inhibition of calcium-induced permeability transition in brain mitochondria. Brain Res 2003;960:99–111PubMedCrossRef
13.
go back to reference Persson L, Hardemark HG, Gustafsson J, et al. S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. Stroke 1987;18:911–918PubMed Persson L, Hardemark HG, Gustafsson J, et al. S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. Stroke 1987;18:911–918PubMed
14.
go back to reference Cunningham RT, Young IS, Winder J, et al. Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction. Eur J Clin Invest 1991;21:497–500PubMedCrossRef Cunningham RT, Young IS, Winder J, et al. Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction. Eur J Clin Invest 1991;21:497–500PubMedCrossRef
15.
go back to reference Loy DN, Sroufe AE, Pelt JL, et al. Serum biomarkers for experimental acute spinal cord injury: rapid elevation of neuron-specific enolase and S-100beta. Neurosurgery 2005;56:391–397PubMedCrossRef Loy DN, Sroufe AE, Pelt JL, et al. Serum biomarkers for experimental acute spinal cord injury: rapid elevation of neuron-specific enolase and S-100beta. Neurosurgery 2005;56:391–397PubMedCrossRef
16.
go back to reference Fischer S, Clauss M, Wiesnet M, et al. Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO. Am J Physiol 1999;276:812–820 Fischer S, Clauss M, Wiesnet M, et al. Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO. Am J Physiol 1999;276:812–820
17.
go back to reference Marchi N, Rasmussen P, Kapural M, et al. Peripheral markers of brain damage and blood-brain barrier dysfunction. Restor Neurol Neurosci 2003;21:109–121PubMed Marchi N, Rasmussen P, Kapural M, et al. Peripheral markers of brain damage and blood-brain barrier dysfunction. Restor Neurol Neurosci 2003;21:109–121PubMed
18.
go back to reference Sullivan PG, Rabchevsky AG, Hicks RR, et al. Dose-response curve and optimal dosing regimen of cyclosporin A after traumatic brain injury in rats. Neuroscience 2000;101:289–295PubMedCrossRef Sullivan PG, Rabchevsky AG, Hicks RR, et al. Dose-response curve and optimal dosing regimen of cyclosporin A after traumatic brain injury in rats. Neuroscience 2000;101:289–295PubMedCrossRef
19.
go back to reference Tachibana T, Shiiya N, Kunihara T, et al. Immunophilin ligands FK506 and cyclosporine A improve neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits. J Thorac Cardiovasc Surg 2005;129:123–128PubMedCrossRef Tachibana T, Shiiya N, Kunihara T, et al. Immunophilin ligands FK506 and cyclosporine A improve neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits. J Thorac Cardiovasc Surg 2005;129:123–128PubMedCrossRef
20.
go back to reference Sato M, Horinouchi T, Sakurai M, et al. Cyclosporin A reduces delayed motor neuron death after spinal cord ischemia in rabbits. Ann Thorac Surg 2003;75:1294–1299PubMedCrossRef Sato M, Horinouchi T, Sakurai M, et al. Cyclosporin A reduces delayed motor neuron death after spinal cord ischemia in rabbits. Ann Thorac Surg 2003;75:1294–1299PubMedCrossRef
21.
go back to reference Mobley LW 3rd, Agrawal SK. Role of calcineurin in calcium-mediated hypoxic injury to white matter. Spine J 2003;3:11–18PubMedCrossRef Mobley LW 3rd, Agrawal SK. Role of calcineurin in calcium-mediated hypoxic injury to white matter. Spine J 2003;3:11–18PubMedCrossRef
22.
go back to reference In JH, Lee JE, Lim YG, et al. Regulation and localization of neuronal nitric oxide synthase in the ischemic rabbit spinal cord. Mol Cells 2003;15:406–411PubMed In JH, Lee JE, Lim YG, et al. Regulation and localization of neuronal nitric oxide synthase in the ischemic rabbit spinal cord. Mol Cells 2003;15:406–411PubMed
23.
go back to reference Diaz-Ruiz A, Vergara P, Perez-Severiano F, et al. Cyclosporin A inhibits constitutive nitric oxide synthase activity and neuronal and endothelial nitric oxide synthase expressions after spinal cord injury in rats. Neurochem Res 2005;30:245–251PubMedCrossRef Diaz-Ruiz A, Vergara P, Perez-Severiano F, et al. Cyclosporin A inhibits constitutive nitric oxide synthase activity and neuronal and endothelial nitric oxide synthase expressions after spinal cord injury in rats. Neurochem Res 2005;30:245–251PubMedCrossRef
Metadata
Title
Effects of Cyclosporin A on Neurological Outcome and Serum Biomarkers in the Same Setting of Spinal Cord Ischemia Model
Authors
Erdem A. Ozkısacık, MD
Berent Discigil, MD
Mehmet Boga, MD
Ugur Gurcun, MD
Muharrem I. Badak, MD
Tunay Kurtoglu, MD
Cigdem Yenısey, MD
Emel Dıkıcıoglu, MD
Publication date
01-03-2006
Publisher
Springer-Verlag
Published in
Annals of Vascular Surgery / Issue 2/2006
Print ISSN: 0890-5096
Electronic ISSN: 1615-5947
DOI
https://doi.org/10.1007/s10016-006-9022-2

Other articles of this Issue 2/2006

Annals of Vascular Surgery 2/2006 Go to the issue