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J Surg Res. 2016 Feb;200(2):655-63. doi: 10.1016/j.jss.2015.10.003. Epub 2015 Oct 8.

CDP-choline modulates matrix metalloproteinases in rat sciatic injury.

Author information

1
Department of Neurosurgery, Uludag University Medical School, Bursa, Turkey.
2
Department of Neurosurgery, Uludag University Medical School, Bursa, Turkey. Electronic address: abekar@uludag.edu.tr.
3
Department of Pharmacology, Uludag University Medical School, Bursa, Turkey.
4
Uludag University Medical School, Bursa, Turkey.
5
Department of Anatomy, Uludag University Medical School, Bursa, Turkey.

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.

MATERIALS AND 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.

KEYWORDS:

Axonal regeneration; CDP-choline; Matrix metalloproteinase; Neuroprotection; Sciatic nerve injury; Tissue inhibitors of metalloproteinases

PMID:
26521098
DOI:
10.1016/j.jss.2015.10.003
[Indexed for MEDLINE]

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