title: CDP-choline modulates matrix metalloproteinases in rat sciatic injury.
abstract: BACKGROUND
  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 CDP-choline with regard to matrix metalloproteinase (MMP) activity in the rat-transected sciatic nerve injury model.
  
  
  METHODS
  Male Wistar rats were randomized into Sham, Saline, and CDP-choline 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 μg/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.
authors.affiliation: Department of Neurosurgery, Uludag University Medical School, Bursa, Turkey.
authors.forename: Elif Basaran
authors.initials: EB
authors.lastname: Gundogdu
authors.affiliation: Department of Neurosurgery, Uludag University Medical School, Bursa, Turkey. Electronic address: abekar@uludag.edu.tr.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bekar
authors.affiliation: Department of Pharmacology, Uludag University Medical School, Bursa, Turkey.
authors.forename: Mesut
authors.initials: M
authors.lastname: Turkyilmaz
authors.affiliation: Uludag University Medical School, Bursa, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Gumus
authors.affiliation: Department of Anatomy, Uludag University Medical School, Bursa, Turkey.
authors.forename: Ilker Mustafa
authors.initials: IM
authors.lastname: Kafa
authors.affiliation: Department of Pharmacology, Uludag University Medical School, Bursa, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cansev
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000201:enzymology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000201:enzymology / Q000293:injuries*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D003566:Cytidine Diphosphate Choline; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Axonal regeneration; CDP-choline; Matrix metalloproteinase; Neuroprotection; Sciatic nerve injury; Tissue inhibitors of metalloproteinases