Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats.
BACKGROUND
Citicoline has been shown to have beneficial effects in a variety of CNS injury models. The aim of this study was to test the effects of citicoline on nerve regeneration and scarring in a rat model of peripheral nerve surgery.


METHODS
Seventy adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve section and epineural suturing. Rats were assigned to the control or experiment groups to receive a topical application of 0.4 mL of saline or 0.4 mL (100 micromol/L) of citicoline, respectively. Macroscopic, histological, functional, and electromyographic assessments of nerves were performed 4 to 12 weeks after surgery.


RESULTS
In the control versus citicoline-treated rats, SFI was -90 +/- 1 versus -84 +/- 1 (P < .001), -76 +/- 4 versus -61 +/- 3 (P < .001), and -66 +/- 2 versus -46 +/- 3 (P < .001) at 4, 8, and 12 weeks after surgery, respectively. At 12 weeks after surgery, axon count and diameter were 16400 +/- 600 number/mm(2) and 5.47 +/- 0.25 microm versus 22250 +/- 660 number/mm(2) (P < .001) and 6.65 +/- 0.28 microm (P < .01) in the control and citicoline-treated groups, respectively. In citicoline-treated rats, histomorphological axonal organization score at the repair site was (3.4 +/- 0.1) significantly better than that in controls (2.6 +/- 0.3) (P < .001). Peripheral nerve regeneration evaluated by EMG at 12 weeks after surgery showed significantly better results in the citicoline group (P < .05). Nerves treated with citicoline demonstrated reduced scarring at the repair site (P < .001).


CONCLUSIONS
Our results demonstrate that citicoline promotes regeneration of peripheral nerves subjected to immediate section suturing type surgery and reduces postoperative scarring.
Özay
Rafet
R
Department of Neurosurgery, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.
Bekar
Ahmet
A
Department of Neurosurgery, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey. Electronic address: abekar@uludag.edu.tr.
Kocaeli
Hasan
H
Department of Neurosurgery, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.
Karlı
Necdet
N
Neurology, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.
Filiz
Gülaydan
G
Neuropathology, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.
Ulus
I Hakkı
IH
Pharmacology, Uludağ University, 16059, Görükle, Bursa, Turkey.
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology; D002921:Cicatrix / Q000517:prevention & control; D003238:Connective Tissue / Q000473:pathology; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D009416:Nerve Regeneration / Q000187:drug effects*; D018697:Nootropic Agents / Q000494:pharmacology*; D011183:Postoperative Complications / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D012584:Sciatic Nerve / Q000293:injuries* / Q000473:pathology / Q000502:physiology / Q000601:surgery
D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline