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Published in: Acta Neurochirurgica 6/2010

01-06-2010 | Experimental research

Citicoline and postconditioning provides neuroprotection in a rat model of ischemic spinal cord injury

Authors: Alper Turkkan, Tulin Alkan, Bulent Goren, Hasan Kocaeli, Eylem Akar, Ender Korfali

Published in: Acta Neurochirurgica | Issue 6/2010

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Abstract

Background

Ischemic spinal cord injury is a chain of events caused by the reduction and/or cessation of spinal cord blood flow, which results in neuronal degeneration and loss. Ischemic postconditioning is defined as a series of intermittent interruptions of blood flow in the early phase of reperfusion and has been shown to reduce the infarct size in cerebral ischemia. Our study aimed to characterize the relationship between the neuronal injury-decreasing effects of citicoline and ischemic postconditioning, which were proven to be effective against the apoptotic process.

Method

Spinal cord ischemia was produced in rats using an intrathoracic approach to implement the synchronous arcus aorta and subclavian artery clipping method. In our study, 42 male Sprague-Dawley rats (309 ± 27 g) were used. Animals were divided into sham operated, spinal ischemia, citicoline, postconditioning, and postconditioning citicoline groups. Postconditioning was generated by six cycles of 1 min occlusion/5 min reperfusion. A 600 mmol/kg dose of citicoline was given intraperitoneally before ischemia in the citicoline and postconditioning citicoline groups. All rats were sacrificed 96 h after reperfusion. For immunohistochemical analysis, bcl-2, caspase 3, caspase 9, and bax immune staining were performed. Caspase 3, caspase 9, bax, and bcl-2 were used as apoptotic and antiapoptotic markers, respectively.

Findings

The blood pressure values obtained at the onset of reperfusion were significantly lower than the preischemic values. A difference in immunohistochemical scoring was detected between the caspase 3, caspase 9, bax, and bcl-2 groups. When comparisons between the ischemia (groups 2, 3, 4, and 5) and sham groups (group 1) were performed, a significant increase in caspase 3, caspase 9, bax, and bcl-2 was detected. When comparing the subgroups, the average score of caspase 9 was found to be significantly higher in ischemia group 2. The average score of bcl-2 was also found to be significantly higher in postconditioning and citicoline group 5.

Conclusions

It is thus thought that combining citicoline with postconditioning provides protection by inhibiting the caspase pathway and by increasing the antiapoptotic proteins.
Literature
1.
go back to reference Bonser RS, Wong CH, Harrington D, Pagano D, Wilkes M, Clutton-Brock T, Faroqui M (2002) Failure of retrograde cerebral perfusion to attenuate metabolic changes associated with hypothermic circulatory arrest. J Thorac Cardiovasc Surg 123:943–950CrossRefPubMed Bonser RS, Wong CH, Harrington D, Pagano D, Wilkes M, Clutton-Brock T, Faroqui M (2002) Failure of retrograde cerebral perfusion to attenuate metabolic changes associated with hypothermic circulatory arrest. J Thorac Cardiovasc Surg 123:943–950CrossRefPubMed
2.
go back to reference Coselli JS, LeMaire SA, Miller CC 3rd, Schmittling ZC, Köksoy C, Pagan J, Curling PE (2000) Mortality and paraplegia after thoracoabdominal aortic aneurysm repair: a risk factor analysis. Ann Thorac Surg 69:409–414CrossRefPubMed Coselli JS, LeMaire SA, Miller CC 3rd, Schmittling ZC, Köksoy C, Pagan J, Curling PE (2000) Mortality and paraplegia after thoracoabdominal aortic aneurysm repair: a risk factor analysis. Ann Thorac Surg 69:409–414CrossRefPubMed
3.
go back to reference Kuniyoshi Y, Koja K, Miyagi K, Shimoji M, Uezu T, Arakaki K, Yamashiro S, Mabuni K, Senaha S, Nakasone Y (2003) Prevention of postoperative paraplegia during thoracoabdominal aortic surgery. Ann Thorac Surg 76:1477–1484CrossRefPubMed Kuniyoshi Y, Koja K, Miyagi K, Shimoji M, Uezu T, Arakaki K, Yamashiro S, Mabuni K, Senaha S, Nakasone Y (2003) Prevention of postoperative paraplegia during thoracoabdominal aortic surgery. Ann Thorac Surg 76:1477–1484CrossRefPubMed
4.
go back to reference Mauney MC, Blackbourne LH, Langenburg SE, Buchanan SA, Kron IL, Tribble CG (1995) Prevention of spinal cord injury after repair of the thoracic or thoracoabdominal aorta. Ann Thorac Surg 59:245–252CrossRefPubMed Mauney MC, Blackbourne LH, Langenburg SE, Buchanan SA, Kron IL, Tribble CG (1995) Prevention of spinal cord injury after repair of the thoracic or thoracoabdominal aorta. Ann Thorac Surg 59:245–252CrossRefPubMed
5.
go back to reference Safi HJ, Miller CC 3rd, Huynh TT, Estrera AL, Porat EE, Winnerkvist AN, Allen BS, Hassoun HT, Moore FA (2003) Distal aortic perfusion and cerebrospinal fluid drainage for thoracoabdominal and descending thoracic aortic repair: ten years of organ protection. Ann Surg 238:372–380PubMed Safi HJ, Miller CC 3rd, Huynh TT, Estrera AL, Porat EE, Winnerkvist AN, Allen BS, Hassoun HT, Moore FA (2003) Distal aortic perfusion and cerebrospinal fluid drainage for thoracoabdominal and descending thoracic aortic repair: ten years of organ protection. Ann Surg 238:372–380PubMed
6.
go back to reference Yamauchi T, Takano H, Nishimura M, Matsumiya G, Sawa Y (2006) Paraplegia and paraparesis after descending thoracic aortic aneurysm repair: a risk factor analysis. Ann Thorac Cardiovasc Surg 12:179–183PubMed Yamauchi T, Takano H, Nishimura M, Matsumiya G, Sawa Y (2006) Paraplegia and paraparesis after descending thoracic aortic aneurysm repair: a risk factor analysis. Ann Thorac Cardiovasc Surg 12:179–183PubMed
7.
go back to reference Giglia JS, Zelenock GB, D’Alecy L (1994) Prevention of paraplegia during thoracic aortic cross-clamping: importance of patent internal mammary arteries. J Vasc Surg 19:1044–1051PubMed Giglia JS, Zelenock GB, D’Alecy L (1994) Prevention of paraplegia during thoracic aortic cross-clamping: importance of patent internal mammary arteries. J Vasc Surg 19:1044–1051PubMed
8.
9.
go back to reference Etz CD, Homann TM, Luehr M, Kari FA, Weisz DJ, Kleinman G, Plestis KA, Griepp RB (2008) Spinal cord blood flow and ischemic injury after experimental sacrifiye of thoracic and abdominal segmental arteries. Eur Jour Cardio-Thoracic Surgery 33(6):1030–1038CrossRef Etz CD, Homann TM, Luehr M, Kari FA, Weisz DJ, Kleinman G, Plestis KA, Griepp RB (2008) Spinal cord blood flow and ischemic injury after experimental sacrifiye of thoracic and abdominal segmental arteries. Eur Jour Cardio-Thoracic Surgery 33(6):1030–1038CrossRef
10.
go back to reference Huang H, Zhang L, Wang Y (2007) Effect of ischemic post-conditioning on spinal cord ischemic-reperfusion injury in rabbits. Can J Anesth 54(1):42–48CrossRefPubMed Huang H, Zhang L, Wang Y (2007) Effect of ischemic post-conditioning on spinal cord ischemic-reperfusion injury in rabbits. Can J Anesth 54(1):42–48CrossRefPubMed
11.
go back to reference Jiang X, Shi E, Li L (2008) Co-application of ischemic preconditioning and postconditioning provides additive neuroprotection against spinal cord ischemia in rabbits. Life Sci 82:608–614CrossRefPubMed Jiang X, Shi E, Li L (2008) Co-application of ischemic preconditioning and postconditioning provides additive neuroprotection against spinal cord ischemia in rabbits. Life Sci 82:608–614CrossRefPubMed
12.
go back to reference Jiang X, Shi E, Nakajima Y, Sato S (2006) Postconditioning, a series of brief interruptions of early reperfusion, prevents neurologic injury after spinal cord ischemia. Ann Surg 244:148–153CrossRefPubMed Jiang X, Shi E, Nakajima Y, Sato S (2006) Postconditioning, a series of brief interruptions of early reperfusion, prevents neurologic injury after spinal cord ischemia. Ann Surg 244:148–153CrossRefPubMed
13.
go back to reference Kanellopoulos GK, Kato H, Hsu CY, Kouchoukos NT (1997) Spinal cord ischemic injury. Development of a new model in the rat. Stroke 28:2532–2538PubMed Kanellopoulos GK, Kato H, Hsu CY, Kouchoukos NT (1997) Spinal cord ischemic injury. Development of a new model in the rat. Stroke 28:2532–2538PubMed
14.
go back to reference Kocaeli H, Korfali E, Oztürk H, Kahveci N, Yilmazlar S (2005) MK-801 improves neurological and histological outcomes after spinal cord ischemia induced by transient aortic cross-clipping in rats. Surg Neurol 64(2):22–27CrossRef Kocaeli H, Korfali E, Oztürk H, Kahveci N, Yilmazlar S (2005) MK-801 improves neurological and histological outcomes after spinal cord ischemia induced by transient aortic cross-clipping in rats. Surg Neurol 64(2):22–27CrossRef
15.
go back to reference Lang-Lazdunski L, Matsushita K, Hirt L, Waeber C, Vonsattel JP, Moskowitz MA, Dietrich WD (2000) Spinal cord ischemia. Development of a model in the mouse. Stroke 31:208–213PubMed Lang-Lazdunski L, Matsushita K, Hirt L, Waeber C, Vonsattel JP, Moskowitz MA, Dietrich WD (2000) Spinal cord ischemia. Development of a model in the mouse. Stroke 31:208–213PubMed
16.
go back to reference Mackey ME, Wu Y, Hu R, DeMaro JA, Jacquin MF, Kanellopoulos GK, Hsu CY, Kouchoukos NT (1997) Cell death suggestive of apoptosis after spinal cord ischemia in rabbits. Stroke 28:2012–2017PubMed Mackey ME, Wu Y, Hu R, DeMaro JA, Jacquin MF, Kanellopoulos GK, Hsu CY, Kouchoukos NT (1997) Cell death suggestive of apoptosis after spinal cord ischemia in rabbits. Stroke 28:2012–2017PubMed
17.
go back to reference Kato H, Kanellopoulos GK, Matsuo S, Wu YJ, Jacquin MF, Hsu CY, Kouchoukos NT, Choi DW (1997) Neuronal apoptosis and necrosis following spinal cord ischemia in the rat. Exp Neurol 148:464–474CrossRefPubMed Kato H, Kanellopoulos GK, Matsuo S, Wu YJ, Jacquin MF, Hsu CY, Kouchoukos NT, Choi DW (1997) Neuronal apoptosis and necrosis following spinal cord ischemia in the rat. Exp Neurol 148:464–474CrossRefPubMed
18.
go back to reference Hayashi T, Sakurai M, Abe K, Sadahiro M, Tabayashi K, Itoyama Y (1998) Apoptosis of motor neurons with induction of caspases in the spinal cord after ischemia. Stroke 29:1007–1013PubMed Hayashi T, Sakurai M, Abe K, Sadahiro M, Tabayashi K, Itoyama Y (1998) Apoptosis of motor neurons with induction of caspases in the spinal cord after ischemia. Stroke 29:1007–1013PubMed
19.
go back to reference Cambria RP, Davison JK, Zannetti S, L'Italien G, Brewster DC, Gertler JP, Moncure AC, LaMuraglia GM, Abbott WM (1997) Clinical experience with epidural cooling for spinal cord protection during thoracic and thoracoabdominal aneurysm repair. J Vasc Surg 25:234–241CrossRefPubMed Cambria RP, Davison JK, Zannetti S, L'Italien G, Brewster DC, Gertler JP, Moncure AC, LaMuraglia GM, Abbott WM (1997) Clinical experience with epidural cooling for spinal cord protection during thoracic and thoracoabdominal aneurysm repair. J Vasc Surg 25:234–241CrossRefPubMed
20.
go back to reference Crawford ES, Svensson LG, Hess KR (1990) A prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high-risk surgery on the thoracoabdominal aorta. J Vasc Surg 13:36–46 Crawford ES, Svensson LG, Hess KR (1990) A prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high-risk surgery on the thoracoabdominal aorta. J Vasc Surg 13:36–46
21.
go back to reference Kouchoukos NT, Masetti P, Rokkas CK, Murphy SF, Blackstone EH (2001) Safety and efficacy of hypotermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta. Ann Thorac Surg 72:699–707CrossRefPubMed Kouchoukos NT, Masetti P, Rokkas CK, Murphy SF, Blackstone EH (2001) Safety and efficacy of hypotermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta. Ann Thorac Surg 72:699–707CrossRefPubMed
22.
go back to reference Adibhatla RM, Hatcher JF, Tureyen K (2005) CDP-choline liposomes provide significant reduction in infarction over free CDP-choline in stroke. Brain Res 5:193–197 Adibhatla RM, Hatcher JF, Tureyen K (2005) CDP-choline liposomes provide significant reduction in infarction over free CDP-choline in stroke. Brain Res 5:193–197
23.
go back to reference de Haan P, Kalkman CJ, Jacobs MJ (2001) Pharmacologic neuroprotection in experimental spinal cord ischemia: a systematic review. J Neurosurg Anesthesiol 13:3–12CrossRefPubMed de Haan P, Kalkman CJ, Jacobs MJ (2001) Pharmacologic neuroprotection in experimental spinal cord ischemia: a systematic review. J Neurosurg Anesthesiol 13:3–12CrossRefPubMed
24.
go back to reference Hurtado O, Moro MA, Cardenas A (2005) Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis 18:336–345CrossRefPubMed Hurtado O, Moro MA, Cardenas A (2005) Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis 18:336–345CrossRefPubMed
25.
go back to reference Krupinski J, Ferrer I, Barrachina M, Secades JJ, Mercadal J, Lozano R (2002) CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat. Neuropharmacology 42:846–854CrossRefPubMed Krupinski J, Ferrer I, Barrachina M, Secades JJ, Mercadal J, Lozano R (2002) CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat. Neuropharmacology 42:846–854CrossRefPubMed
26.
go back to reference Secades JJ, Lorenzo LJ (2006) Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Pharmacol 27:1–56 Secades JJ, Lorenzo LJ (2006) Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Pharmacol 27:1–56
27.
go back to reference Ulus IH, Watkins CJ, Cansev M (2006) Cytidine and üridine increase striatal CDP-choline levels without decreasing acetylcholine synthesis or release. Cell Mol Neurobiol 26:563–577CrossRefPubMed Ulus IH, Watkins CJ, Cansev M (2006) Cytidine and üridine increase striatal CDP-choline levels without decreasing acetylcholine synthesis or release. Cell Mol Neurobiol 26:563–577CrossRefPubMed
28.
go back to reference Zhao ZQ, Corvera JS, Halkos ME (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:579–588 Zhao ZQ, Corvera JS, Halkos ME (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:579–588
29.
go back to reference Zhao H (2008) The protective effect of ischemic postconditioning against ischemic injury: from the heart to the brain. J Neuroimmune Pharmacol 2:313–318CrossRef Zhao H (2008) The protective effect of ischemic postconditioning against ischemic injury: from the heart to the brain. J Neuroimmune Pharmacol 2:313–318CrossRef
30.
go back to reference Burda J, Matiasova M, Gottlieb M (2005) Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region. Neurochem Res 30:1397–1405CrossRefPubMed Burda J, Matiasova M, Gottlieb M (2005) Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region. Neurochem Res 30:1397–1405CrossRefPubMed
31.
go back to reference Taskapilioglu MO, Alkan T, Goren B, Tureyen K, Sahin S, Taskapilioglu O, Korfali E (2008) Neuronal protective effects of focal ischemic pre-and/or postconditioning on 4 the model of transient focal cerebral ischemia in rats. J Clin Neurosci 1010-1016 Taskapilioglu MO, Alkan T, Goren B, Tureyen K, Sahin S, Taskapilioglu O, Korfali E (2008) Neuronal protective effects of focal ischemic pre-and/or postconditioning on 4 the model of transient focal cerebral ischemia in rats. J Clin Neurosci 1010-1016
32.
go back to reference Zhao H, Sapolsky RM, Steinberg GK (2006) Interrupting reperfusion as a stroke theraphy: ischemic postconditioning reduces infarct size after focal ischemia in ras. J Cereb Blood Flow Metab 26:1114–1122CrossRefPubMed Zhao H, Sapolsky RM, Steinberg GK (2006) Interrupting reperfusion as a stroke theraphy: ischemic postconditioning reduces infarct size after focal ischemia in ras. J Cereb Blood Flow Metab 26:1114–1122CrossRefPubMed
33.
go back to reference LeMay DR, Neal S, Neal S, Zelenock GB, D'Alecy LG (1987) Paraplegia in the rat induced by aortic cross-clamping: model characterization and glucose exacerbation of neurologic deficit. J Vasc Surg 6:383–390CrossRefPubMed LeMay DR, Neal S, Neal S, Zelenock GB, D'Alecy LG (1987) Paraplegia in the rat induced by aortic cross-clamping: model characterization and glucose exacerbation of neurologic deficit. J Vasc Surg 6:383–390CrossRefPubMed
34.
35.
go back to reference Zivin JA, DeGirolami U, Hurwitz EL (1982) Spectrum of neurological deficits in experimental CNS ischemia: a quantitative study. Arch Neurol 39:408–412PubMed Zivin JA, DeGirolami U, Hurwitz EL (1982) Spectrum of neurological deficits in experimental CNS ischemia: a quantitative study. Arch Neurol 39:408–412PubMed
36.
go back to reference Lang-Lazdunski L, Heurteaux C, Dupont H, Rouelle D, Widmann C, Mantz J (2001) The effects of FK506 on neurological and histopathologic outcome after transient spinal cord ischemia induced by aortic crossclamping in rats. Anesth Analg 92:1237–1244CrossRefPubMed Lang-Lazdunski L, Heurteaux C, Dupont H, Rouelle D, Widmann C, Mantz J (2001) The effects of FK506 on neurological and histopathologic outcome after transient spinal cord ischemia induced by aortic crossclamping in rats. Anesth Analg 92:1237–1244CrossRefPubMed
37.
go back to reference Adibhatla RM, Hatcher JF (2006) Phospholipase A2, reactive oxygen species and lipid peroxidation in cerebral ischemia. Free Radic Biol Med 40:376–387CrossRef Adibhatla RM, Hatcher JF (2006) Phospholipase A2, reactive oxygen species and lipid peroxidation in cerebral ischemia. Free Radic Biol Med 40:376–387CrossRef
38.
go back to reference Aronowski J, Labiche LA (2003) Perspectives on reperfusion-induced damage in rodent models of experimental focal ischemia and role of protein kinase C. ILAR 44:105–109 Aronowski J, Labiche LA (2003) Perspectives on reperfusion-induced damage in rodent models of experimental focal ischemia and role of protein kinase C. ILAR 44:105–109
39.
go back to reference Aronowski J, Strong R, Grotta JC (1997) Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab 17:1048–1056CrossRefPubMed Aronowski J, Strong R, Grotta JC (1997) Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab 17:1048–1056CrossRefPubMed
40.
go back to reference Hermann DM, Matter CM (2007) Tissue plasminogen activator-induced reperfusion injury after stroke revisited. Circulation 116:363–365CrossRefPubMed Hermann DM, Matter CM (2007) Tissue plasminogen activator-induced reperfusion injury after stroke revisited. Circulation 116:363–365CrossRefPubMed
41.
go back to reference Saito A, Maier CM, Narasimhan P, Nishi T, Song YS, Yu F, Liu J, Lee YS, Nito C, Kamada H, Dodd RL, Hsieh LB, Hassid B, Kim EE, González M, Chan PH (2005) Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Mol Neurobiol 31:105–116CrossRefPubMed Saito A, Maier CM, Narasimhan P, Nishi T, Song YS, Yu F, Liu J, Lee YS, Nito C, Kamada H, Dodd RL, Hsieh LB, Hassid B, Kim EE, González M, Chan PH (2005) Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Mol Neurobiol 31:105–116CrossRefPubMed
42.
go back to reference Takamatsu H, Tsukada H, Kakiuchi T, Nishiyama S, Noda A, Umemura K (2000) Detection of reperfusion injury using PET in a monkey model of cerebral ischemia. J Nucl Med 41:1409–1416PubMed Takamatsu H, Tsukada H, Kakiuchi T, Nishiyama S, Noda A, Umemura K (2000) Detection of reperfusion injury using PET in a monkey model of cerebral ischemia. J Nucl Med 41:1409–1416PubMed
43.
go back to reference Watson BD, Prado R, Veloso A, Brunschwig JP, Dietrich WD (2002) Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke. Stroke 33:428–434CrossRefPubMed Watson BD, Prado R, Veloso A, Brunschwig JP, Dietrich WD (2002) Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke. Stroke 33:428–434CrossRefPubMed
44.
go back to reference Danielisová V, Némethová M, Gottlieb M, Burda J (2005) Changes of endogenous antioxidant enzymes during ischemic tolerance acquisition. Neurochem Res 30:559–565CrossRefPubMed Danielisová V, Némethová M, Gottlieb M, Burda J (2005) Changes of endogenous antioxidant enzymes during ischemic tolerance acquisition. Neurochem Res 30:559–565CrossRefPubMed
45.
go back to reference Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM (2004) Postconditioning: a form of “modified reperfusion” protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res 95:230–232CrossRefPubMed Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM (2004) Postconditioning: a form of “modified reperfusion” protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res 95:230–232CrossRefPubMed
46.
go back to reference Xing B, Chen H, Zhang M, Zhao D, Jiang R, Liu X, Zhang S (2008) Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat. Stroke 39:2362–2369CrossRefPubMed Xing B, Chen H, Zhang M, Zhao D, Jiang R, Liu X, Zhang S (2008) Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat. Stroke 39:2362–2369CrossRefPubMed
47.
go back to reference Adibhatla RM, Hatcher JF, Dempsey RJ (2002) Citicoline: neuroprotective mechanism in cerebral ischemia. J Neurochem 80:12–23CrossRefPubMed Adibhatla RM, Hatcher JF, Dempsey RJ (2002) Citicoline: neuroprotective mechanism in cerebral ischemia. J Neurochem 80:12–23CrossRefPubMed
48.
go back to reference Adibhatla RM, Hatcher JF, Larsen EC, Chen X, Sun D, Tsao FH (2006) CDP-choline significantly restores phosphatidylcholine levels by differentially affecting phospholipase A2 and CTP: phosphocholine cytidylyltransferase after stroke. J Biol Chem 281:6718–6725CrossRefPubMed Adibhatla RM, Hatcher JF, Larsen EC, Chen X, Sun D, Tsao FH (2006) CDP-choline significantly restores phosphatidylcholine levels by differentially affecting phospholipase A2 and CTP: phosphocholine cytidylyltransferase after stroke. J Biol Chem 281:6718–6725CrossRefPubMed
49.
go back to reference Cakir E, Usul H, Peksoylu B, Sayin OC, Alver A, Topbas M, Baykal S, Kuzeyli K (2005) Effects of citicoline on experimental spinal cord injury. J Clin Neurosci 12(8):923–926CrossRefPubMed Cakir E, Usul H, Peksoylu B, Sayin OC, Alver A, Topbas M, Baykal S, Kuzeyli K (2005) Effects of citicoline on experimental spinal cord injury. J Clin Neurosci 12(8):923–926CrossRefPubMed
50.
go back to reference Fiedorowicz M, Makarewicz D, Stańczak-Mrozek KI, Grieb P (2008) CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia. Acta Neurobiol Exp 68:389–397 Fiedorowicz M, Makarewicz D, Stańczak-Mrozek KI, Grieb P (2008) CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia. Acta Neurobiol Exp 68:389–397
51.
go back to reference Yücel N, Caylı SR, Ateş O (2006) Evaluation of the neuroprotective effects of citicoline after experimental spinal cord injury: improved behavioral and neuroanatomical recovery. Neurochem Res 31:767–775CrossRefPubMed Yücel N, Caylı SR, Ateş O (2006) Evaluation of the neuroprotective effects of citicoline after experimental spinal cord injury: improved behavioral and neuroanatomical recovery. Neurochem Res 31:767–775CrossRefPubMed
52.
go back to reference Başkaya MK, Doğan A, Rao AM, Dempsey RJ (2000) Neuroprotective effects of citicoline on brain edema and blood-brain barrier breakdown after traumatic brain injury. J Neurosurg 92:448–452CrossRefPubMed Başkaya MK, Doğan A, Rao AM, Dempsey RJ (2000) Neuroprotective effects of citicoline on brain edema and blood-brain barrier breakdown after traumatic brain injury. J Neurosurg 92:448–452CrossRefPubMed
53.
go back to reference Takagi T, Takayasu M, Mizuno M, Yoshimoto M, Yoshida J (2003) Caspase activation in neuronal and glial apoptosis following spinal cord injury in mice. Neurol Med Chir 43:20–30CrossRef Takagi T, Takayasu M, Mizuno M, Yoshimoto M, Yoshida J (2003) Caspase activation in neuronal and glial apoptosis following spinal cord injury in mice. Neurol Med Chir 43:20–30CrossRef
Metadata
Title
Citicoline and postconditioning provides neuroprotection in a rat model of ischemic spinal cord injury
Authors
Alper Turkkan
Tulin Alkan
Bulent Goren
Hasan Kocaeli
Eylem Akar
Ender Korfali
Publication date
01-06-2010
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 6/2010
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-010-0598-5

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