Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats

Özay, Rafet; Bekâr, Ahmet; Kocaelı, Hasan; Karlı, Necdet; Filiz, Gülaydan; Ulus, İsmail H.

doi:10.1016/j.surneu.2006.12.054

Cited by 50 publications

(38 citation statements)

References 44 publications

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“…Similar findings were also observed in a previous study, though these results were limited by extensive swelling and collapse of the biomaterial poly(lactic co-glycolic acid) (PLGA) in the study. CMAP examinations offer an important index for the conduction function of peripheral nerve [2,[28][29][30][31]. In this study, we observed the highest CMAP amplitude of autograft repair in both plantar foot muscles and dorsal muscles.…”

Section: Discussionsupporting

confidence: 58%

Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit

et al. 2010

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Single channel conduits are used clinically in nerve repair as an alternative to the autologous nerve graft.Axons regenerating across single channel tubes, however, may disperse resulting in inappropriate target reinnervation. This dispersion may be limited by multichannel nerve conduits as they resemble the structure of nerve multiple basal lamina tubes. In this study, we investigated the influence of channel number on the axonal regeneration using a series of 1-, 2-, 4-, and 7-channel collagen conduits and commercial (NeuraGen ® ) single channel conduits. Nerve conduits were implanted in rats with a 1cm gap of sciatic nerve.After four months, quantitative results of regeneration were evaluated with nerve morphometry and the accuracy of regeneration was assessed using retrograde tracing: two tracers being applied simultaneously to tibial and peroneal nerves to determine the percentage of motor neurons with double projections. Recovery of function was investigated with compound muscle action potential recordings and ankle motion analysis. We showed that the fabricated 1-channel and 4-channel conduits are superior to other types of conduits in axonal regeneration. Simultaneous tracing showed a significantly lower percentage of motor neurons with double projections after 2-and 4-channel compared with 1-channel conduit repair. This study shows the potential influence of multichannel guidance on limiting dispersion without decreasing quantitative results of regeneration.

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Section: Discussionsupporting

confidence: 58%

Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit

et al. 2010

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“…Citicoline has been suggested to reduce brain injury in both experimental and clinical studies (2). In a previous study from our laboratory, we reported that topically-administered citicoline after primary saturation following peripheral nerve incision significantly increased axonal regeneration by preventing scar tissue formation (31). We determined, in a follow-up study (6) that was designed to investigate the effects of topically-administered citicoline, as well as its metabolites cytidine, choline, and cytidine plus choline following sciatic nerve incision and primary anastomosis that cytidine plus choline was as efficient as citicoline in reducing scar tissue formation and increasing functional recovery by potentiating axonal regeneration.…”

Section: Figure 5: Graphs Depicting Mean Density (A) and Total Numbermentioning

confidence: 84%

“…In a previous study performed in our laboratory (31) topical citicoline was shown to decrease perineural scar tissue and to increase axonal regeneration as well as functional recovery in rats undergoing primary repair following peripheral nerve damage. In a follow-up study, we examined the effects of topically-administered citicoline, cytidine, choline, and cytidine plus choline in a primary anastomosis model of the sciatic nerve and found that cytidine plus choline and citicoline were efficient in preventing scar tissue formation and that cytidine plus choline increased the functional recovery by potentiating axonal regeneration (6).…”

Section: Introductionmentioning

confidence: 85%

Investigation of the dose-dependency of citicoline effects on nerve regeneration and functional recovery in a rat model of sciatic nerve injury

Kaplan¹,

Kafa²,

Cansev³

et al. 2013

Turkish Neurosurgery

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AIm:The aim of this study was to investigate the dose dependence of citicoline's previously-reported effects on recovery of peripheral nerve injury. mAterIAl and methOds: Right sciatic nerves of sixty adult female Wistar Albino rats were incised and primary anastomosis was performed. Rats were then divided into four groups: Control group received 2 ml of saline intraperitoneally, while rats in C-300, C-600 and C-900 groups received 300 μmol/kg, 600 μmol/kg and 900 μmol/kg citicoline dissolved in 2 ml saline, respectively. Rats were tested for sciatic functional index (SFI) on the 4th, 8th and 12th weeks and electrophysiological recordings were obtained on the 12th week. Rats were then sacrificed to investigate nerve adhesions and perform histomorphological examinations. results:Our results showed that rats in C-600 and C-900 groups had significantly lesser neural adhesion and greater SFI and electrophysiological score than those in the Control and C-300 groups (p<0.05). Mean density and total number of functionally myelinated axons were significantly increased in C-900 group, while perineural scar tissue formation was reduced in all citicoline-treated groups. COnClusIOn:We conclude that citicoline exhibits dose-dependent effects on axonal regeneration and recovery without scar formation in a rat model of peripheral nerve incision and primary anastomosis.

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“…Data obtained in our previous studies on citicoline's effects on promoting regeneration of peripheral nerves subjected to immediate section suturing type surgery and reducing postoperative scarring, and recent similar observations encouraged us to test citicoline in prevention of epidural fibrosis after lumbar disc surgery (6,12,36). Hence, the purpose of our study was to investigate local and systemic effectiveness of citicoline on epidural fibrosis in a rat model of laminotomy and discectomy.…”

Section: Savran M Et Al: Prevention Of Epidural Fibrosis In Ratsmentioning

confidence: 85%

Prevention of epidural fibrosis in rats by local or systemic administration of citicoline

Savran¹,

Bekâr²,

Cansev³

et al. 2012

Turkish Neurosurgery

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AIm: The objective of this study was to investigate the effect of citicoline administration on epidural fibrosis which is a frequent complication of lumbar disc surgery with no effective treatment or preventive surgical technique. mATeRIAL and meTHods: Sixty Sprague-Dawley female rats undergoing L4-5 right hemilaminotomy and annular fenestration were arranged in three groups: rats in Group 1 (control group) and Group 2 (topical citicoline group) were applied 0,9% saline and 100 µM citicoline on surgical area, respectively, while rats in Group 3 (systemic citicoline group) received 600 µmol/kg citicoline intraperitoneally. Rats were sacrificed four weeks later and their vertebral colons were removed en bloc. Groups were evaluated according to histological criteria and results were compared using statistical tools. ResuLTs:Compared with control group, significantly less epidural fibrosis, dural adhesion, fibroblast cell density, foreign body reaction, and medulla spinalis retraction were observed in groups treated with topical and systemic citicoline (groups 2 and 3) (p<0,001). No significant difference was found with regard to measured parameters between two treatment groups (p>0,05). CoNCLusIoN:Our study demonstrates for the first time in the literature that citicoline may be effective for preventing postoperative epidural fibrosis. However, its mechanism of action and clinical effectiveness must be further investigated.KeywoRds: Epidural fibrosis, Annular fenestration, Laminatomy, Citicoline, Rat ÖZ AmAÇ: Çalışmamızın amacı, sitikolin uygulamasının henüz efektif bir tedavisi veya koruyucu bir cerrahi tekniği bulunmayan ve lomber disk cerrahisinin sık bir komplikasyonu olan epidural fibrozis üzerine etkisini incelemektir. yÖNTem ve GeReÇLeR: Sağ L4-5 hemilaminatomive anular fenestrasyonu yapılmış 60 Spraque Dawley dişi sıçan 3 gruba ayrıldı. Grup 1 (kontrol grubu) ve Grup 2 (topikal sitikolin grubu)'deki sıçanlara cerrahi alan üzerine sırasıyla 0,9% serum fizyolojik ve 100 µM sitikolin uygulanırken, Grup 3 (sistemik sitikolin grubu)'deki sıçanlara intraperitoneal yolla 600 µmol/kg sitikolin verildi. Sıçanlar 4 hafta sonra öldürüldü ve vertebral kolonları blok olarak çıkarıldı. Gruplar histolojik kriterlere göre değerlendirildi ve sonuçlar istatistiksel yöntemler kullanılarak karşılaştırıldı.BuLGuLAR: Topikal ve sistemik sitikolin ile tedavi edilen (Grup 2 ve 3) gruplarda kontrol grubuna kıyasla istatistiksel olarak daha az epidural fibrozis, dural yapışıklık, fibroblast hücre yoğunluğu, yabancı cisim reaksiyonu ve medulla spinalis retraksiyonu gözlendi (p<0,001). İncelenen parametreler bakımından iki tedavi grubu arasında anlamlı bir fark bulunmadı (p>0,05). soNuÇ: Çalışmamız literatürde ilk kez sitikolin'in postoperatif epidural fibrozisi önlemede efektif olabileceğini göstermiştir. Ancak sitikolinin etki mekanizmaları ve klinik etkinliği ilerideki çalışmalarla araştırılmalıdır.

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Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats

Cited by 50 publications

References 44 publications

Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit

Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit

Investigation of the dose-dependency of citicoline effects on nerve regeneration and functional recovery in a rat model of sciatic nerve injury

Prevention of epidural fibrosis in rats by local or systemic administration of citicoline

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