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.
Department of Neurosurgery, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.
Rafet
R
Özay
Department of Neurosurgery, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey. Electronic address: abekar@uludag.edu.tr.
Ahmet
A
Bekar
Department of Neurosurgery, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.
Hasan
H
Kocaeli
Neurology, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.
Necdet
N
Karlı
Neuropathology, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.
Gülaydan
G
Filiz
Pharmacology, Uludağ University, 16059, Görükle, Bursa, Turkey.
I Hakkı
IH
Ulus
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