Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model - PubMed (original) (raw)
Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model
M Andersen et al. Stroke. 1999 Jul.
Abstract
Background and purpose: We sought to evaluate the effects of the combination of cytidine-5'-diphosphocholine (citicoline) and thrombolysis on infarct size, clinical outcome, and mortality in a rat embolic stroke model.
Methods: Eighty-three Sprague-Dawley rats were embolized in the carotid territory with a single fibrin embolus and randomly assigned to the following treatment groups: (1) control (saline), (2) citicoline 250 mg/kg, (3) citicoline 500 mg/kg, (4) recombinant tissue plasminogen activator (rtPA) 5 mg/kg, (5) rtPA 5 mg/kg plus citicoline 250 mg/kg, and (6) rtPA 5 mg/kg plus citicoline 500 mg/kg. rtPA was administered as a continuous intravenous infusion over 45 minutes starting 45 minutes after embolization; citicoline was given intraperitoneally 30 minutes and 24, 48, and 72 hours after embolization. At 96 hours, the brains were fixed and stained by hematoxylin-eosin, and infarct volumes were measured. Neurological scores were determined daily.
Results: The median infarct size, measured as percentage of the affected hemisphere, in the control group was 37% (interquartile range, 26% to 69%) compared with 22% (5% to 52%; P=NS) in group 2, 11% (5% to 34%; P=NS) in group 3, 24% (12% to 31%; P=NS) in group 4, 11% (3% to 22%; P=0.02) in the combined group 5, and 19% (9% to 51%; P=NS) in group 6. The infarct size was significantly reduced in the combined citicoline+rtPA-treated groups to a median of 13% (5% to 30%; P<0.01). Citicoline 500 mg/kg and citicoline combined with rtPA also promoted functional recovery.
Conclusions: These results demonstrate that the combination of low-dose citicoline and rtPA significantly reduced infarct size in this focal ischemia model.
Similar articles
- Effect of combined therapy with thrombolysis and citicoline in a rat model of embolic stroke.
Alonso de Leciñana M, Gutiérrez M, Roda JM, Carceller F, Díez-Tejedor E. Alonso de Leciñana M, et al. J Neurol Sci. 2006 Sep 25;247(2):121-9. doi: 10.1016/j.jns.2006.03.022. Epub 2006 Jun 22. J Neurol Sci. 2006. PMID: 16797595 - Synergistic effects of a combination of low-dose basic fibroblast growth factor and citicoline after temporary experimental focal ischemia.
Schäbitz WR, Li F, Irie K, Sandage BW Jr, Locke KW, Fisher M. Schäbitz WR, et al. Stroke. 1999 Feb;30(2):427-31; discussion 431-2. doi: 10.1161/01.str.30.2.427. Stroke. 1999. PMID: 9933283 - Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase bcl-2 expression after focal cerebral ischemia.
Sobrado M, López MG, Carceller F, García AG, Roda JM. Sobrado M, et al. Neuroscience. 2003;118(1):107-13. doi: 10.1016/s0306-4522(02)00912-0. Neuroscience. 2003. PMID: 12676142 - Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials.
Secades JJ, Alvarez-Sabín J, Castillo J, Díez-Tejedor E, Martínez-Vila E, Ríos J, Oudovenko N. Secades JJ, et al. J Stroke Cerebrovasc Dis. 2016 Aug;25(8):1984-96. doi: 10.1016/j.jstrokecerebrovasdis.2016.04.010. Epub 2016 May 24. J Stroke Cerebrovasc Dis. 2016. PMID: 27234918 Review. - [Thrombolytic therapy of brain infarct: the end of beginning].
Stam J, Koudstaal PJ, Franke CL, Kappelle LJ, Boiten J. Stam J, et al. Ned Tijdschr Geneeskd. 2000 May 27;144(22):1028-32. Ned Tijdschr Geneeskd. 2000. PMID: 10850103 Review. Dutch.
Cited by
- Magnesium in stroke treatment.
Muir KW. Muir KW. Postgrad Med J. 2002 Nov;78(925):641-5. doi: 10.1136/pmj.78.925.641. Postgrad Med J. 2002. PMID: 12496316 Free PMC article. Review. - Investigational therapies for ischemic stroke: neuroprotection and neurorecovery.
Sahota P, Savitz SI. Sahota P, et al. Neurotherapeutics. 2011 Jul;8(3):434-51. doi: 10.1007/s13311-011-0040-6. Neurotherapeutics. 2011. PMID: 21604061 Free PMC article. Review. - Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy.
Sun MS, Jin H, Sun X, Huang S, Zhang FL, Guo ZN, Yang Y. Sun MS, et al. Oxid Med Cell Longev. 2018 Jan 31;2018:3804979. doi: 10.1155/2018/3804979. eCollection 2018. Oxid Med Cell Longev. 2018. PMID: 29770166 Free PMC article. Review. - Clinical trials for cytoprotection in stroke.
Labiche LA, Grotta JC. Labiche LA, et al. NeuroRx. 2004 Jan;1(1):46-70. doi: 10.1602/neurorx.1.1.46. NeuroRx. 2004. PMID: 15717007 Free PMC article. Review. - Multimodal neuroprotective therapy with induced hypothermia after ischemic stroke.
Hemmen TM, Lyden PD. Hemmen TM, et al. Stroke. 2009 Mar;40(3 Suppl):S126-8. doi: 10.1161/STROKEAHA.108.533083. Epub 2008 Dec 8. Stroke. 2009. PMID: 19064802 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous