2023-03-072023-03-072015-10-01Gündoğdu, E. B. vd. (2016). "CDP-choline modulates matrix metalloproteinases in rat sciatic injury". Journal of Surgical Research, 200(2), 655-663.0022-48041095-8673https://doi.org/10.1016/j.jss.2015.10.003https://www.sciencedirect.com/science/article/pii/S002248041500949Xhttp://hdl.handle.net/11452/31386Background: CDP-choline (cytidine-5'-diphosphocholine) improves functional recovery, promotes nerve regeneration, and decreases perineural scarring in rat peripheral nerve injury. The aim of the present study was to investigate the mechanism of action of CDPcholine with regard to matrix metalloproteinase (MMP) activity in the rat-transected sciatic nerve injury model. Materials and methods: Male Wistar rats were randomized into Sham, Saline, and CDPcholine groups. Rats in Sham group received Sham surgery, whereas rats in Saline and CDP-choline groups underwent right sciatic nerve transection followed by immediate primary saturation and injected intraperitoneally with 0.9% NaCl (1 mL/kg) and CDP-choline (600 mg/kg), respectively. Sciatic nerve samples were obtained 1, 3, and 7 d after the surgery and analyzed for levels and activities of MMP-2 and MMP-9, levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-3, and axonal regeneration. Results: CDP-choline treatment decreased the levels and activities of MMP-2 and MMP-9, whereas increasing levels of TIMP-1 and TIMP-3 significantly on the third and seventh day after injury compared to Saline group. In addition, CDP-choline administration resulted in new axon formation and formation and advancement of myelination on newly formed islets (compartments) of axonal regrowth. Conclusions: Our data show, for the first time, that CDP-choline modulates MMP activity and promotes the expression of TIMPs to stimulate axonal regeneration. These data help to explain one mechanism by which CDP-choline provides neuroprotection in peripheral nerve injury.eninfo:eu-repo/semantics/closedAccessSurgeryCDP-cholineSciatic nerve injuryMatrix metalloproteinaseTissue inhibitors of metalloproteinasesAxonal regenerationNeuroprotectionPeripheral-nerve surgeryFunctional recoveryExtracellular-matrixRegenerationCytidineModelMetabolitesExpressionSystemInvolvementAnimalsBiomarkersBlotting, westernCytidine diphosphate cholineInjections, intraperitonealMaleMatrix metalloproteinase 2Matrix metalloproteinase 9Nerve regenerationNeuroprotective agentsPeripheral nerve injuriesRandom allocationRatsRats, wistarSciatic nerveTissue inhibitor of metalloproteinase-1Tissue inhibitor of metalloproteinase-3Article0003668415000302-s2.0-84982268812655663200226521098SurgeryCiticoline; Brain Ischemia; GlycerylphosphorylcholineCiticolineGelatinase AGelatinase BMatrix metalloproteinaseScleroproteinSodium chlorideTissue inhibitor of metalloproteinase 1Tissue inhibitor of metalloproteinase 3Biological markerCiticolineGelatinase AGelatinase BMmp2 protein, ratMmp9 protein, ratNeuroprotective agentTissue inhibitor of metalloproteinase 1Tissue inhibitor of metalloproteinase 3Tissue inhibitor of metalloproteinase-1 protein, ratAnimal cellAnimal experimentAnimal modelAnimal tissueArticleCell densityControlled studyDown regulationDrug mechanismEnzyme activityExperimental sciatic nerve injuryMaleMyelinationNerve transectionNervous tissueNeurite outgrowthNeuroprotectionNonhumanPerineuriumPriority journalProtein expression levelRatUpregulationZymographyAnimalDrug effectsEnzymologyEvaluation studyInjuriesIntraperitoneal drug administrationMetabolismNerve regenerationPeripheral nerve injuriesPhysiologyRandomizationSciatic nerveWestern blottingWistar rat