Synergistic effects of citicoline and MK-801 in temporary experimental focal ischemia in rats
| Autor: | Fuhai Li, Bobby W. Sandage, M. Zülküf Önal, Turgut Tatlisumak, Marc Fisher, Kenneth W. Locke |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Cytidine Diphosphate Choline
medicine.medical_treatment Ischemia Central nervous system disease Rats Sprague-Dawley chemistry.chemical_compound Bolus (medicine) Medicine Choline Animals Saline Advanced and Specialized Nursing Chemotherapy business.industry Antagonist Drug Synergism Cerebral Infarction medicine.disease Survival Analysis Rats Neuroprotective Agents chemistry Ischemic Attack Transient Anesthesia Neurology (clinical) Dizocilpine Maleate Cardiology and Cardiovascular Medicine business Excitatory Amino Acid Antagonists Citicoline medicine.drug |
| Zdroj: | Stroke. 28(5) |
| ISSN: | 0039-2499 |
| Popis: | Background and Purpose Citicoline, a naturally occurring precursor of phosphatidylcholine, is neuroprotective and is currently being assessed in clinical trials. To evaluate potential synergistic neuroprotective effects of prolonged citicoline treatment and early N -methyl- d -aspartate (NMDA) antagonist therapy, suboptimal treatment regimens of citicoline and MK-801 were tested alone and in combination in a rat model of temporary focal ischemia. Methods Four groups of Sprague-Dawley rats (n=12 per group) underwent 90 minutes of temporary middle cerebral artery occlusion (MCAO) with the suture model. Animals were randomly and blindly assigned to one of four treatment groups: (1) saline, vehicle; (2) MK-801, 0.5 mg/kg IV bolus at 60 minutes after MCAO followed by saline 1 mL/kg IP daily for 7 days; (3) saline IV at 60 minutes after MCAO followed by citicoline 250 mg/kg IP daily for 7 days; or (4) both MK-801 and citicoline (daily for 7 days) active treatment. Triphenyltetrazolium chloride staining was used to assess postmortem infarct volume. Neurological scores were determined daily. Results Premature mortality between days 2 and 4 was 33.3% in group 1, 41.7% in groups 2 and 3, and 25.0% in group 4. Mean corrected infarct volume was significantly reduced in group 4 compared with the others (175.2±89.3 mm 3 in group 1, 179.1±78.5 mm 3 in group 2, 163.9±73.7 mm 3 in group 3, and 84.7±56.8 mm 3 in group 4 [ P P P t test) larger in group 1 than those surviving for 7 days (247.2±89.5 versus 139.2±68.2 mm 3 ), but there was no significant difference in infarct volume in groups 2, 3, and 4 between animals dying prematurely and those surviving for 7 days. Conclusions These results demonstrate synergistic neuroprotective effects of citicoline and an NMDA antagonist in temporary experimental focal ischemia. |
| Databáze: | OpenAIRE |
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