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In Alzheimers disease, Citicoline may inhibit the deposition of beta-amyloid, a neurotoxic protein involved in the pathophysiology of the disease [5]. Role of Citicoline in Treatment of Newborns With Hypoxic Ischemic Neurohabilitation 26(1):513 Neurol Res. The mean mRS scores for the four groups were 3.1 for placebo, 2.5 for the 500 mg citicoline group, 3.1 for the 1000 mg citicoline group, and 2.6 for the 2000 mg citicoline group [30]. Kobayashi T, Uchino H, Elmr E, Ogihara Y, Fujita H, Sekine S, Ishida Y, Saiki I, Shibata S, Kawachi A. Int J Mol Sci. Twenty newborns fulfilling the inclusion criteria were selected for the study and and F.P. The results indicated a higher density or RGC connected with the superior colliculus in those treated with Citicoline compared with the others. After assessment for eligibility, 47 studies were included in the qualitative synthesis. Three months after starting treatment, the patients condition was assessed using the NIHSS and mRS scales. Iranmanesh F., Vakilian A. (Armonk, NY: IBM Corp). It was observed that on day 1 after surgery, the activity of metalloproteinases 2 and 9 increased to a similar extent in the control group and that receiving citicoline. The next study focused on citicoline combined with the effect of drinking on behavior control and executive functions. Citicoline use, regardless of the age of the respondents, was an independent factor improving the quality of life and was beneficial for patients after stroke. Part of However, one sizeable multicenter study undermined the efficacy of citicoline and showed its uncertain effectiveness. In the human body, citicoline is degraded to cytidine and choline during hydrolysis and dephosphorylation. PubMed Central Griffiths mental development scales (GMDS): are used for the neurodevelopmental assessment of the included infants. Subjects had an electroencephalography (EEG) taken in repose and during an examination. In the EPT test, the groups receiving citicoline had a significantly lower percentage of a motor deficit than in the control group: for 0.4 and 0.8 mL, respectively, 14.28% and 20.6% (p = 0.00). Various pathological conditions can lead to damage to peripheral nerves and the occurrence of neuropathic pain. ; project administration, K.R. The results went back to the baseline levels after washout period. OR for the meta-analysis by Secades et al. There are several treatment options used now for HIE as xenon, erythropoietin, melatonin, and stem cell therapy. To find articles, the following keywords were used: citicoline, neurology disorders, CDP-choline, and cytidine-5-diphosphocholine. Citicoline in this study proved unsuccessful. [26]. Bethesda, MD 20894, Web Policies The data was fed to the computer and analyzed using IBM SPSS software package version 20.0. Das S.K., Ghosh S., Nath T., Ghosh K.C., Bhattacharyya R., Mondal G.P. Alvarez et al. In the United States, they are the leading cause of disability in people under 45 and account for 30.5% of all injury-related deaths [58]. After 28 days, the NIHSS result in the research group was 9.43, while in the control group, it was 14.56 (p < 0.05). The most important features of research cited above are summarized in the table (Table 3). Citicoline contributed to the reduction of both per-accident and long-term mortality. Accessibility The oxidative metabolism of arachidonic acid contributes to the generation of neuroinflammation and reactive oxygen species (ROS). It can be bought as a tablet or an injection. Bull Exp Biol Med. Citicoline in hypoxic ischemic encephalopathy in neonates: a randomized controlled trial, https://doi.org/10.1186/s13052-023-01452-5, https://clinicaltrials.gov/ct2/show/NCT03949049, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, Neonatology Italian Society of Neonatology (SIN). The last substance to be tested was angiostatin, which is an anti-angiogenic substance. Given the nationwide choline gap and limited food sources of choline/CDP-choline, citicoline has a place in every brain-friendly routine. There are also common cell death mechanisms of glaucoma and neurological progressive diseases [16]. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Shokouhi G., Haghjoo A.G., Sattarnezhad N., Asghari M., Sattarnezhad A., Asghari A., Pezeshki A. Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. A higher percentage (42%) of citicoline-treated patients had improvement compared with patients receiving placebo (30%) (p = 0.01). 2021;180(4):124955. ; resources, F.P. The number of trials needed to solve the test perfectly was also significantly lower in the test group (p = 0.028). With the aging of the population, the problem of nerve damage will become more frequent and require new treatments. Iranmanesh et al. A GQ of90 was considered normal, 8089 was mild disability, 7079 was moderate disability, and<70 was severe disability [14]. In 2006, Gupta first demonstrated the presence of degenerative changes in lateral geniculate nucleus and visual cortex in glaucoma patients. Some authors demonstrated the neuroprotective role of Citicoline in glutamate-mediated cell death by using a model of Kainic acid (KA)-induced retinal damage in rats, which is an analogue of glutamate. Cacabelos R, Caamao J, Gmez MJ, Fernndez-Novoa L, Franco-Maside A, Alvarez XA. The results persisted after the wash out period, compared to baseline. 8600 Rockville Pike Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats. In the next study, rats after sciatic nerve injury were divided into five groups: control, receiving citicoline, cytidine, choline, and cytidine + choline. A total of 2706 patients from twelve controlled-trials were included in the meta-analysis, which was performed by Secades [62]. Parisi V. Electrophysiological assessment of glaucomatous visual dysfunction during treatment with cytidine-5-diphosphocholine (citicoline): A study of 8 years of follow-up. VEP measurement showed an improvement of conduction along the visual pathways. Cranial ultrasound and MRI findings at 4weeks were significantly better in the treatment group compared to the control group. 1. These are essential functions in everyday situations. 2009;26:92539. Yu C., Zelterman D. A parametric meta-analysis. Article Cranial ultrasound scanning and MRI brain in our study showed better results in the citicoline treated group compared to the control group after 4weeks of treatment. Choline, one of the breakdown products of citicoline, serves as a substrate for the synthesis of acetylcholine. The role of citicoline in neuroprotection and neurorepair in ischemic stroke. However, in the 18th month, the discrepancy between results was bigger (23.12 vs. 21.49; p < 0.05). After being absorbed, cytidine and choline are re-phosphorylated, and Citicoline is recreated from choline monophosphate and cytidine triphosphate. J Neurotrauma. The effectiveness of citicoline in TBI treatment is not entirely clear. Data are available from the corresponding author on reasonable requested. All children meeting the inclusion criteria were randomly assigned to one of the two groups: The citicoline treatment group: included 40 neonates with HIE who received citicoline 10mg /kg /12h IV within 6h of admission for 4weeks plus other supportive measures (including mechanical ventilation, inotropic support, and phenoparbitone for management of seizures if needed) in the NICU [12]. Improvement was noted in 32% and 18% on Day 7, and 54% and 29% on Day 14, for the citicoline and placebo groups, respectively. There were no significant differences between the groups in the SFI test (p = 0.26). The mean flow velocity was significantly different between the right internal carotid (p = 0.031) and left anterior cerebral artery groups (p = 0.033); the measured speeds were also lower in the citicoline group. [51], the effect of the drug on memory was assessed in healthy volunteers. The influence of citicoline on the level of metalloproteinases may explain its beneficial effect in the regeneration of damaged peripheral nerves [70]. Citicoline in the dose of 2 mol increased the pain threshold to 150 g, and this effect lasted for several hours (p < 0.001). The global effect of citicoline and the effect of each citicoline dose on the individual scales are shown in Figures 1 . In a study by Sobrino et al. Cognitive functions were assessed using the Cognitive Emotional Regulation Questionnaire (CERQ), and impulsivity and attention were assessed using the Test of Variables of Attention (TOVA). On Days 2, 7, and 14, the GIR of the citicoline group was significantly better than that of the placebo group. Citicoline Benefits & Side Effects: Everything You Need To Know premium form) in the full-potency, clinically studied dose of 500 milligrams. In this test, the subject has to tap the button with a selected finger as fast as possible during a specific time. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimers disease patients. To assess motor functions, the Finger Tap Test was conducted. Abdulqawi K, Al-Zohairy YZ, Karam K. Early predictors of neurodevelopmental adverse outcome in term infants with post asphyxial hypoxic ischemic encephalopathy. The contrast sensitivity and the visual evoked potential also improved. CDP-Choline is a mononucleotide made of ribose, pyrophosphate, cytosine and choline, and its chemical structure is illustrated in Fig. The tests were performed initially, after 30 days (at the end of citicoline administration), and after 60 days. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, citicoline, neurology, supplementation, treatment. Article 3) [19]. Similarly, on the BI scale, people from the research group obtained better results (69.28 vs. 51.57) (p < 0.05). The SFI values as an indicator of functional recovery were significantly better in rats treated with citicoline than those in rats treated with saline. Acute or chronic IOP elevation can cause a blockade of the axonal transport of neurotrophins from the superior colliculus to the optic nerve head. Citicoline is necessary for the synthesis of cell membrane. The Geriatric Depression Scale (GDS) is used in depression assessment. zay R., Bekar A., Kocaeli H., Karl N., Filiz G., Ulus .H. Kaplan T., Kafa I.M., Cansev M., Bekar A., Karl N., Taskapilioglu M.O., Kanar F. Investigation of the dose-dependency of citicoline effects on nerve regeneration and functional recovery in a rat model of sciatic nerve injury. and A.R. All of the analyzed articles noted thus far indicated that citicoline is an effective drug in the improvement of the clinical condition of patients after stroke. government site. This test assesses, among others, memory, attention, and decision-making abilities. Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke. Comparison of the Effects of Citicoline and Piracetam on Hypoxic 2002;87:10910. The study was registered at ClinicalTrials.gov (NCT03949049). Von Frey filaments (threshold 100 g) were used to assess neuropathic pain. other medical conditions you have. Post-resuscitation brain injury is one of the major complications that can lead to death or disability. Exogenous Citicoline, administered by ingestion or injection, is hydrolyzed and dephosphorylated in order to form cytidine and choline, which resynthesize CDP-choline inside brain cells. PLoS ONE. Overgaard K. The effects of citicoline on acute ischemic stroke: a review. Citicoline is globally available as a dietary supplement and in many countries as a drug. The Rotterdam CT score, Glasgow Coma Scale (GCS), and the Injury Severity Score (ISS) were used to initially assess the condition of patients after trauma. Aslan E., Kocaeli H., Bekar A., Tolunay S., Ulus I.H. 2021;31(12):15112. Clark W.M., Warach S.J., Pettigrew L.C., Gammans R.E., Sabounjian L.A. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Contraindications Contraindications have not been identified. Healthy older patients participated in the study. After 12 weeks, no significant increase in PDE levels was observed compared to those taking citicoline. Saver JL. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimers disease patients. Inclusion in an NLM database does not imply endorsement of, or agreement with, and A.R. Clark W.M., Wechsler L.R., Sabounjian L.A., Schwiderski U.E. The last can describe the structures that contribute to the visual function. There was a significant reduction in the number of neonates having seizures after discharge in the citicoline-treated group (2 neonates) compared to the control group (11 neonates). Choline liberated from Citicoline can be metabolized to glutathione, one of the most important endogenous antioxidant defense systems in the brain. SIRT1 belongs to the histone deacetylase family. In an experimental study, Citicoline has been detected in the vitreous when administered topically [25]. Arch Dis Child. 2010;2(6):1125. Alive neonates were sacrificed after 10 minutes of exposure to a high dose of pentobarbitone (1 g, Specia, France). https://doi.org/10.1186/s13052-023-01452-5, DOI: https://doi.org/10.1186/s13052-023-01452-5. There was a significant treatment effect seen with the logistic regression analysis comparing citicoline treatments to placebo at 12 weeks (p 0.05). Local ethics committee of Faculty of Medicine, Tanta University approved the study. Another important aspect is the usage of such compounds to enhance natural abilities in school and work. Full recovery (BI 95) after 12 weeks was completed in 33% of patients from the placebo group, 53% from 500 mg, 29% from 1000 mg, and 45% from the 2000 mg group. Park CH, Kim YS, Noh HS, Cheon EW, Yang YA, Yoo JM, Choi WS, Cho GJ. However, on day 21 of follow-up, patients in the citicoline group achieved significantly better SSS scores (49.2 and 44.7 points, respectively, p = 0.017). The treatment group had a mean GA of 38.31.8weeks, a mean birth weight of 2990670g, and they were 20 males and 20 females, while the control group had a mean GA of 38.11.7weeks, a mean birth weight of 2850590g, and they were 27 males and 13 females. Citicoline may also show anti-apoptotic effects [18]. Federal government websites often end in .gov or .mil. HHS Vulnerability Disclosure, Help Patients treated with citicoline achieved significantly higher BI scores both in the 1st and 3rd month (p < 0.001 in 1st month, p = 0.002 in 3rd month). Citicoline enhances neuroregenerative process after experimental stroke in rats. The Citicoline-treated group showed an improvement of VEP and ERGp parameters when compared to placebo that was treatment-dependent. In amblyopia, Citicoline may improve the retinal and postretinal visual pathways by stimulating the dopaminergic system. sharing sensitive information, make sure youre on a federal Their level correlates with the ability to regenerate damaged nerves. Citicoline Dosage. The company estimated that its injection could prevent up to 500,000 medical visits a year . Cytidine and choline are the two parts of Citicoline connected by a diphosphate bridge. The Continuous Performance Task (CPT), which was used in the evaluation of concentration, memory, and impulse control, was used in the study. Iulia C, Ruxandra T, Costin LB, Liliana-Mary V. Rom J Ophthalmol. Gndodu E.B., Bekar A., Turkyilmaz M., Gumus A., Kafa I.M., Cansev M. CDP-choline modulates matrix metalloproteinases in rat sciatic injury. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Nichol G, Thomas E, Callaway CW, Hedges J, Powell JL, Aufderheide TA, Rea T, Lowe R, Brown T, Dreyer J et al (2008) Regional variation in out-of-hospital cardiac arrest incidence and outcome. Moreover, we preferred 4weeks for scanning by MRI rather than 2weeks secondary to some technical difficulties like transportation of mechanically ventilated children as some patients enrolled in the study were mechanically ventilated and others were too unwell and unstable to be scanned within the first weeks after birth. Allen KA, Brandon DH. Another study assessed the effects of citicoline on cognition with the CogState Battery. Accessibility Citicoline for acute ischemic stroke in Mexican hospitals: a retrospective postmarketing analysis. Besides acetylcholine, it also boosts norepinephrine and dopamine in the brain [ 4, 6 ]. The advantage of the following study is its longer period of stroke patient observation. Twenty newborns fulfilling the inclusion criteria were selected for the study and were given injection citicoline via the IV route. Barthel Index (BI); National Institute of Health Stroke Scale (NIHSS); modified Rankin Scale (mRS); Scandinavian Stroke Scale (SSS); The Japanese Coma Scale (JCS); Global Improvement Rating(GIR); magnetic resonance imaging (MRI). Student t-test was used to compare two groups for normally distributed quantitative variables. The frequency of incidences of non-neurological complications during hospitalization was also analyzed. Serum lactate, brain magnetic resonance imaging and outcome of neonatal hypoxic ischemic encephalopathy after therapeutic hypothermia. There was statistically significant reduction in the duration of seizures, NICU stay, inotrope use, and MV in the treatment group compared to the control group. Salamah, A., El Amrousy, D., Elsheikh, M. et al. Schuettauf F, Rejdak R, Thaler S, Bolz S, Lehaci C, Mankowska A, Zarnowski T, Junemann A, Zagorski Z, Zrenner E, et al. Infants who experience moderate HIE have a 10% risk of fatality, and those who live have a 30% risk of disabilities. After 90 days from the start of treatment, the mean improvement in the GOS-E score in the research group was 35.4%, and in the control group, it was 35.6%. The OR for improvement in BI on citicoline 500 mg treatment was 2.0, and on 2000 mg, it was 2.1. National Library of Medicine Department of Neurology, Medical University of Lublin, 20-059 Lublin, Poland; Received 2020 Aug 5; Accepted 2020 Oct 9.

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