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dc.contributor.authorSchabitz, Wolf-Rudiger
dc.contributor.authorLi, Fuhai
dc.contributor.authorIrie, Katsumi
dc.contributor.authorSandage, Bobby W.
dc.contributor.authorLocke, Kenneth W.
dc.contributor.authorFisher, Marc
dc.date2022-08-11T08:09:35.000
dc.date.accessioned2022-08-23T16:36:36Z
dc.date.available2022-08-23T16:36:36Z
dc.date.issued1999-02-05
dc.date.submitted2009-03-31
dc.identifier.citationStroke. 1999 Feb;30(2):427-31; discussion 431-2.
dc.identifier.issn0039-2499 (Print)
dc.identifier.pmid9933283
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38822
dc.description.abstractBACKGROUND AND PURPOSE: Basic fibroblast growth factor (bFGF) and citicoline (cytidine 5'-diphosphate choline, an endogenous compound that stabilizes membrane function) have demonstrated neuroprotective effects after focal cerebral ischemia. Both agents are candidates for future stroke therapy in humans. For evaluation of synergistic effects of bFGF and citicoline, a low-dose combination of both compounds was tested against each compound alone and placebo. METHODS: Four groups of Sprague-Dawley rats (n=12 per group) underwent 90 minutes of focal cerebral ischemia with the use of the suture model of middle cerebral artery occlusion. Animals were randomly and blindly assigned to one of the following treatment groups: placebo, low-dose citicoline (250 mg/kg IP daily for 4 days), low-dose bFGF (10 microg/kg per hour IV for 3 hours), and the combination of both (250 mg/kg citicoline and 10 microg/kg per hour bFGF). Triphenyltetrazolium chloride staining was used after 4 days to determine postmortem infarction. Neurological scores were assessed on a daily basis. RESULTS: The premature mortality rate was 41.7% in the placebo and citicoline groups, 33.3% in the bFGF group, and 25% (P=NS) in the combination group. The mean neurological score on day 4 was 3.1+/-1.6 (placebo), 3.1+/-1.6 (citicoline), 2.9+/-1.5 (bFGF), and 2.4+/-1.4 (combination) (P=NS). The mean volume of infarction was significantly reduced in the combination group (136. 5+/-25.4 mm3) versus placebo (172.6+/-48.9 mm3; P=0.036, Fisher test), versus citicoline alone (186.0+/-35.7 mm3; P=0.005, Fisher test), and versus bFGF alone (176.0+/-49.2 mm3; P=0.023, Fisher test). CONCLUSIONS: These results demonstrate synergistic effects of a low-dose combination of the growth factor bFGF and citicoline after temporary experimental focal cerebral ischemia and furthermore support the effectiveness of a combination treatment regimen for the management of acute stroke.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9933283&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAnimals
dc.subjectCerebral Infarction
dc.subjectCytidine Diphosphate Choline
dc.subjectDose-Response Relationship, Drug
dc.subjectDrug Synergism
dc.subjectDrug Therapy, Combination
dc.subjectFibroblast Growth Factor 2
dc.subjectFollow-Up Studies
dc.subjectInfusions, Intravenous
dc.subjectIschemic Attack, Transient
dc.subjectMale
dc.subjectNootropic Agents
dc.subjectRandom Allocation
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectTreatment Outcome
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleSynergistic effects of a combination of low-dose basic fibroblast growth factor and citicoline after temporary experimental focal ischemia
dc.typeJournal Article
dc.source.journaltitleStroke; a journal of cerebral circulation
dc.source.volume30
dc.source.issue2
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2663&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1664
dc.identifier.contextkey805485
refterms.dateFOA2022-08-23T16:36:36Z
html.description.abstract<p>BACKGROUND AND PURPOSE: Basic fibroblast growth factor (bFGF) and citicoline (cytidine 5'-diphosphate choline, an endogenous compound that stabilizes membrane function) have demonstrated neuroprotective effects after focal cerebral ischemia. Both agents are candidates for future stroke therapy in humans. For evaluation of synergistic effects of bFGF and citicoline, a low-dose combination of both compounds was tested against each compound alone and placebo. METHODS: Four groups of Sprague-Dawley rats (n=12 per group) underwent 90 minutes of focal cerebral ischemia with the use of the suture model of middle cerebral artery occlusion. Animals were randomly and blindly assigned to one of the following treatment groups: placebo, low-dose citicoline (250 mg/kg IP daily for 4 days), low-dose bFGF (10 microg/kg per hour IV for 3 hours), and the combination of both (250 mg/kg citicoline and 10 microg/kg per hour bFGF). Triphenyltetrazolium chloride staining was used after 4 days to determine postmortem infarction. Neurological scores were assessed on a daily basis. RESULTS: The premature mortality rate was 41.7% in the placebo and citicoline groups, 33.3% in the bFGF group, and 25% (P=NS) in the combination group. The mean neurological score on day 4 was 3.1+/-1.6 (placebo), 3.1+/-1.6 (citicoline), 2.9+/-1.5 (bFGF), and 2.4+/-1.4 (combination) (P=NS). The mean volume of infarction was significantly reduced in the combination group (136. 5+/-25.4 mm3) versus placebo (172.6+/-48.9 mm3; P=0.036, Fisher test), versus citicoline alone (186.0+/-35.7 mm3; P=0.005, Fisher test), and versus bFGF alone (176.0+/-49.2 mm3; P=0.023, Fisher test). CONCLUSIONS: These results demonstrate synergistic effects of a low-dose combination of the growth factor bFGF and citicoline after temporary experimental focal cerebral ischemia and furthermore support the effectiveness of a combination treatment regimen for the management of acute stroke.</p>
dc.identifier.submissionpathoapubs/1664
dc.contributor.departmentDepartment of Neurology
dc.source.pages427-31; discussion 431-2


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