Effect Of Citicoline Research Articles

The citicoline effect of choroidal and scleral thickness in Rattus norvegicus myopia model: A preliminary study

This preliminary study aim to analyze the effect of citicoline to the scleral and choroidal thickness in rattus norvegicus myopia model. This study used lens induced myopia (LIM) method, by giving -10.00 D lens that framed with rubber ring for 3 weeks. The using of ruber as a lens frame has more complication risk than silicone frame. The 300 mg/kgBW citicoline treatment group increase the posterior segment od scleral and choroidal thickness. It could be concluded that citicoline could change the average scleral and choroidal thickness in rattus novergicus myopia model.

Neuroprotective effects induced by citicoline/coenzyme Q10 fixed combination in rat CTX-TNA2 astrocytes exposed to oxidative stress

The present study aimed to investigate the rationale and efficacy of testing endogenous substances widely used as dietary supplement such as citicoline, coenzyme Q10 (CoQ10) and a fixed combination of them in countering the oxidative stress and neurotoxicity occurring in neurological diseases. Rat CTX-TNA2 astrocytes, which have considerable antioxidant potential and could represent a key target for neurotherapies were selected as in vitro model to conduct the experiments. The efficacy of citicoline and coenzyme Q10 (1 nM-10 μM), with their fixed combination, were assayed in rat astrocytes either in basal condition or after challenging the cells with hydrogen peroxide in order to evaluate the biocompatibility of treatments. The gene expression of B-Cell Lymphoma protein 2 (BCL-2), BCL-2 Associated X (BAX), Superoxide dismutase 2 (SOD2), Cardiolipin Synthase 1 (CRLS1), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) involved in neurodegenerative diseases and neuroinflammation were investigated in CTX-TNA2 cells. Furthermore, in the same condition, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was carried out to assess apoptosis in astrocytes. Neither citicoline, nor coenzyme Q10 significantly altered astrocytes cell viability; thus, suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study. Moreover, each compound tested alone or in combination were effective in inhibiting the hydrogen peroxide-induced gene expression of BAX, and SOD2, in inducing the gene expression of BCL-2 and CRLS1 and in reducing apoptosis. The blunting effects induced by the abovementioned treatments on hydrogen-peroxide induced apoptosis was also confirmed by TUNEL assay that demonstrated the capability of citicoline, CoQ10, and their combination to reduce the ratio TUNEL positive nuclei/total nuclei, a reliable marker of apoptosis. Additionally, citicoline, CoQ10, and their association were effective in inhibiting the hydrogen peroxide-induced NFkB, TNFα, and IL-6 gene. In parallel, there was an inhibition of both TNFα and IL-6 gene expression in basal condition. The co-administration of citicoline/coenzyme Q10 was overall more effective than individual ingredients. The present findings support the beneficial and synergistic effects of citicoline and coenzyme Q10 in fixed combination in reducing oxidation, and in stimulating neuroprotection in rat CTX-TNA2 astrocytes.

Citicoline: A Cholinergic Precursor with a Pivotal Role in Dementia and Alzheimer's Disease.

Citicoline is a naturally occurring compound with pleiotropic effects on neuronal function and cognitive processes. Based on previous studies, which shed light on the positive effects of citicoline 1 g when combined with acetylcholinesterase inhibitors (AChEIs) and/or memantine, we further investigated the benefits of citicoline in combination therapy in Alzheimer's disease and mixed dementia. We integrated the datasets of CITIMEM and CITIDEMAGE, increasing the overall sample size to enhance statistical power. We analyzed data from these two investigator-initiated studies involving 295 patients. The primary outcome was the assessment over time of the effects of combined treatment versus memantine given alone or AChEI plus memantine on cognitive functions assessed by Mini-Mental State Examination (MMSE). The secondary outcomes were the influence of combined treatment on daily life functions, mood, and behavioral symptoms assessed by activities of daily life (ADL) and instrumental ADL, Geriatric Depression Scale, and Neuropsychiatric Inventory Scale. One-hundred-forty-three patients were treated with memantine and/or AChEI (control group), and 152 patients were treated with memantine and/or AChEI plus citicoline 1 g/day orally (Citicoline group). A significant difference in MMSE score was found in the average between the two groups of treatment at 6 and 12 months. This study confirmed the effectiveness of combined citicoline treatment in patients with mixed dementia and Alzheimer's disease, with a significant effect on the increase of MMSE score over time. The treated group also showed a significant reduction in the Geriatric Depression Scale and a significant increase in the instrumental ADL scale.

'Citicoline' and support of the memory function: Evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006.

Following an application from Egde Pharma Sp. z o.o, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Poland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to citicoline and memory. The Panel considers that the food, citicoline (cytidine 5-diphosphocholine, CDP-Choline) inner salt, is sufficiently characterised. Improvement, maintenance or reduced loss of memory is a beneficial physiological effect for middle-aged or elderly adults encountering age-associated subjective memory impairment. The applicant identified three pertinent human intervention studies in healthy individuals that investigated the effect of citicoline on memory. In weighing the evidence, the Panel took into account that only one randomised controlled trial in healthy participants showed a beneficial effect of citicoline on episodic memory when consumed at doses of 500 mg/day for 12 weeks, whereas this effect has not been observed in another study using citicoline at doses of 1 g/day for 3 months or supported by data obtained in patients with dementia using doses of 1 g/day for 12 weeks and 12 months. No convincing evidence of a plausible mechanism by which citicoline or any of its components (in addition to their endogenous synthesis) could exert an effect on memory in humans has been provided. The Panel concludes that a cause-and-effect relationship has not been established between the consumption of citicoline (CDP-Choline) inner salt and improvement, maintenance or reduced loss of memory in middle-aged or elderly adults encountering age-associated subjective memory impairment.

The role of citicoline in the correction of cerebral blood flow disorders in patients with coronary artery disease in combination with COVID-19

OBJECTIVE. To evaluate the effect of citicoline on cerebral blood flow and microembolic signals (MES) after 6 months of treatment in patients with coronary artery disease combined with coronavirus disease (COVID-19). MATERIALS AND METHODS. A prospective study of 68 patients with coronary artery disease with confirmed COVID-19 by PCR was conducted. Group I (n=35) included patients with coronary artery disease in combination with COVID-19, who, in addition to standard therapy of cerebrovascular disease, received citicoline (500 mg twice daily) for 6 months after discharge from the hospital. The comparison group (group II; n=33) consisted of patients who did not receive citicoline. Cerebral blood flow, peak systolic velocity in extracranial and intracranial vessels were determined, and 1-hour transcranial monitoring to detect MES were performed. Patients were re-examined in 6 months. RESULTS. At the initial examination of patients, cerebral blood flow and the number of MES did not differ significantly. After 6 months, there was an increase in cerebral blood flow in the cerebral arteries, as well as a decrease in MES in patients taking citicoline, whereas in group II there was no positive dynamics of this ratio. A direct correlation between plasma C-reactive protein, D-dimer and MES was found in patients of both groups. After 6 months of treatment, C-reactive protein and D-dimer decreased in both groups equally. CONCLUSIONS. The obtained results of improvement of cerebral perfusion, blood rheology, due to the anti-inflammatory effect, stabilising function of citicoline on phospholipid membranes of cerebral vascular endothelium, neurons and glial elements allow the use of citicoline in patients with coronary artery disease in combination with COVID-19 to reduce the negative impact of COVID-19 on the central nervous system.

Possibility of correction of cerebral blood flow disorders and central nervous system damage with citicoline in patients with coronary artery disease in combination with COVID-19

ABSTRACT. The review describes some pathogenetic mechanisms of central nervous system lesions in patients with coronary artery disease in combination with coronavirus disease (COVID-19) and presents the current possibilities of their pharmacotherapy. The analysis of experimental and clinical trials has shown that the multifactorial effect of citicoline on the main pathogenic links of brain damage in COVID-19 and numerous positive clinical effects make it a promising drug in the treatment of patients with coronary artery disease in combination with COVID-19 and post-COVID syndrome.

Additive anxiolytic-like effect of citicoline and ACPA in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice

The cannabinoid system plays a key role in stress-related emotional symptoms such as anxiety. Citicoline is a supplemental substance with neuroprotective properties that alleviates anxiety-related behaviors. There is a relation between the actions of cannabinoids and cholinergic systems. So, we decided to evaluate the effects of intracerebroventricular (i.c.v.) infusion of cannabinoid CB1 receptor agents on citicoline-produced response to anxiety-like behaviors in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice. For i.c.v. microinjection of drugs, a guide cannula was inserted in the left lateral ventricle. ARS was induced by movement restraint for 4 h. Anxiety-related behaviors were assessed using an elevated plus maze (EPM). The results showed that induction of ARS for 4 h decreased the percentage of time spent in the open arms (%OAT) and the percentage of entries to the open arms (%OAE) without affecting locomotor activity, showing anxiogenic-like behaviors. i.c.v. infusion of ACPA (1 µg/mouse) induced an anxiolytic-like effect due to the enhancement of %OAT in the NARS and ARS mice. Nonetheless, i.c.v. microinjection of AM251 (1 µg/mouse) decreased %OAT in the NARS and ARS mice which suggested an anxiogenic-like response. Intraperitoneal (i.p.) administration of citicoline (80 mg/kg) induced an anxiolytic-like effect by the augmentation of %OAT in the ARS mice. Furthermore, when ACPA and citicoline were co-administrated, ACPA potentiated the anxiolytic-like effect induced by citicoline in the NARS and ARS mice. On the other hand, when AM251 and the citicoline were co-injected, AM251 reversed the anxiolytic-like response induced by the citicoline in the NARS and ARS mice. The results of this research exhibited an additive effect between citicoline and ACPA on the induction of anxiolytic-like response in the NARS and ARS mice. Our results indicated an interaction between citicoline and cannabinoid CB1 receptor drugs on the control of anxiety-like behaviors in the NARS and ARS mice.

Synergistic effects of citicoline and silymarin nanomicelles in restraint stress-exposed mice

This study evaluated the effects of citicoline and silymarin nanomicelles (SMnm) in repeated restraint stress (RRS). MethodMice were exposed to RRS for four consecutive days, 2 hrs. daily. On day 5 of the study, SMnm (25 and 50 mg/kg, i.p.) and citicoline (25 and 75 mg/kg), and a combination of them (25 mg/kg, i.p.) were initiated. On day 18, anxiety-like behavior, behavioral despair, and exploratory behavior were evaluated. The prefrontal cortex (PFC) and the hippocampus were dissected measuring brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and tumor necrosis factor-alpha (TNF-α) through Western Blot and ELISA, respectively. ResultsIn RR-exposed mice, anxiety-like behavior in the elevated plus maze (EPM) was enhanced by reductions in open arm time (OAT%) P < 0.001, and open arm entry (OAE%) P < 0.001. In the forced swimming test (FST), the immobility increased P < 0.001 while the swimming and climbing reduced P < 0.001. In the open field test (OFT), general motor activity was raised P < 0.05. Further, body weights reduced P < 0.001, and tissue BDNF and pCREB expressions decreased P < 0.001 while TNF-α increased P < 0.001. Conversely, SMnm, citicoline and their combination could reduce anxiety-like behavior P < 0.001. The combination group reduced the depressive-like behaviors P < 0.001. Moreover, body weights were restored P < 0.001. Besides, BDNF and pCREB expressions increased while TNF-α reduced, P < 0.001. ConclusionThe combination synergistically improved emotion-like behaviors, alleviating the inflammation and upregulating the hippocampal BDNF-mediated CREB signaling pathway.

Protective Effect of Citicoline on Sodium Arsenite-Induced Nephrotoxicity in Mice

Background: Sodium arsenite (NaAsO2) is a common mineral contaminant in drinking water in numerous parts of the world. It has been shown to have cardiovascular, metabolic, neuroendocrine, and urinary effects on the body. There is abundant scientific evidence that establishes a strong correlation between arsenic exposure and kidney-related disorders. Objectives: The present study aimed to investigate the potential protective effect of citicoline against NaAsO2-induced nephrotoxicity. Methods: The groups included a control group, a group treated with NaAsO2 at a concentration of 50 ppm, a group treated with Cit at a dosage of 1000 mg/kg, and three groups of NaAsO2 (50 ppm) co-treated with Cit at doses of 250, 500, and 1000 mg/kg, respectively. Results: Citicoline decreased the level of blood urea nitrogen (P &lt; 0.001), creatinine levels (P &lt; 0.001), thiobarbituric acid reactive substances (P &lt; 0.001), nitric oxide (P &lt; 0.001), inflammatory factors tumor necrosis factor-α (P &lt; 0.001) and interleukin-6 (P &lt; 0.001 and P &lt; 0.001). Furthermore, Cit increased total thiol (P &lt; 0.001) and activity levels of catalase (P &lt; 0.05 and P &lt; 0.001), superoxide dismutase (P &lt; 0.01 and P &lt; 0.001), and glutathione peroxidase (P &lt; 0.001). Therefore, Cit reduced the harmful effects caused by the imbalance in oxidative and antioxidant systems and histopathological damage in NaAsO2-intoxicated mice, improving the damage caused by oxidative stress and inflammation. Conclusions: Our research shows that Cit can protect the kidneys against the damaging effects of NaAsO2 by using its antioxidant and anti-inflammatory properties.

The emerging role of α7nAChRs/caspase-3/Nrf-2 signaling pathway in citicoline improved autistic behavior induced by thimerosal in mice

AimsAutism spectrum disorder (ASD) is a global concern,affecting around 75 million individuals.Various factors contribute to ASD,including mercury-containing preservatives like thimerosal (Thim) found in some vaccines.This study explored whether citicoline could be a therapeutic option for Thim-induced neuronal damage in a mouse model of ASD.Additionally,the study investigated the effects of citicoline on the α7nAChRs/Akt/Nrf2/caspase-3 pathway,which may be involved in the development of ASD. Materials and methodsThe study separated newborn mice into four groups.The control group received saline injections,while the Thim group received intramuscular injections of 3000 μg Hg/kg Thim on days 7,9,11,and 15 after birth.The two citicoline groups were administered Thim followed by intraperitoneal injections of 250 mg/kg or 500 mg/kg citicoline for three weeks.Afterward,various parameters were assessed, including growth,behavior,brain histopathology,oxidative stress,apoptotic,and inflammatory markers. Key findingsUntreated Thim-exposed mice exhibited significant brain damage,which was substantially alleviated by citicoline treatment.This beneficial effect was associated with increased expressions and concentrations of brain α7nAChRs and Akt, increased brain content of Nrf2, and the hippocampus contents of acetylcholine. Citicoline treatment decreased the brain levels of oxidative stress markers (MDA and NO),the apoptotic marker caspase-3,and pro-inflammatory markers (NF-κB,TNF-α,and IL-1β). The drug also increased the brain GPx activity. SignificanceBased on the results of this study,the α7nAChRs pathway appears to be essential for the therapeutic effectiveness of citicoline in treating Thim-induced ASD in mice.

Synergistic antidepressant-like effect of citicoline and CB 1 agonist in male mice.

The endocannabinoid system plays a key role in the control of many emotional-correlated reactions such as stress, depressed mood, and anxiety. Moreover, citicoline has neuroprotective properties and indicates beneficial effects in the treatment of depressive problems. Acute restraint stress (ARS) is an experimental model used for the induction of rodent models of depression. This research was designed to assess the effects of intracerebroventricular (i.c.v.) injection of cannabinoid CB1 receptor agents on citicoline-induced response to depression-like behaviors in the non-acute restraint stress (NARS) and ARS mice. For i.c.v. microinjection, a guide cannula was implanted in the left lateral ventricle of male mice. The ARS model was carried out by movement restraint for 4 h. Depression-related behaviors were assessed by forced swimming test (FST), tail suspension test (TST), and splash test. The results exhibited that the ARS mice showed depressive-like responses. I.c.v. infusion of ACPA (1 μg/mouse) induced an antidepressant-like effect in the NARS and ARS mice by reduction of immobility time in the FST and TST as well as enhancement of grooming activity time in the splash test. On the other hand, i.c.v. microinjection of AM251 dose-dependently (0.5 and 1 μg/mouse) induced a depressant-like effect in the NARS mice. I.p. injection of citicoline (80 mg/kg) induced an antidepressant-like response in the NARS and ARS mice. Furthermore, ACPA (0.25 μg/mouse, i.c.v.) potentiated the antidepressant-like response induced by citicoline (20 mg/kg, i.p.) in the NARS and ARS mice. However, AM251 (0.25 μg/mouse, i.c.v.) reversed the antidepressant-like effect produced by the citicoline (80 mg/kg, i.p.) in the NARS and ARS mice. Interestingly, our results indicated a synergistic effect between citicoline and ACPA based on the induction of an antidepressant-like effect in the NARS and ARS mice. These results suggested an interaction between citicoline and cannabinoid CB1 receptors on the modulation of depression-like behaviors in the NARS and ARS mice.

Use of Citicoline in Attention-Deficit/Hyperactivity Disorder: A Pilot Study.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurobehavioral disorder in school-aged children. Although there are several drug treatment options, some patients do not have adequate therapeutic responses to conventional medications or experience considerable adverse effects. Citicoline is an endogenous molecule that has beneficial effects on attention, impulsivity, and memory and is a potential treatment for ADHD. This study aimed to evaluate the effect of citicoline in pediatric patients diagnosed with ADHD. This randomized, crossover, double-blind, placebo-controlled clinical trial included with patients aged 7-12 years diagnosed with ADHD. As a result, no statistically significant difference was noted between the use of citicoline and placebo in the evaluated parameters. The treatment had no adverse effects. Citicoline seems to be a safe molecule to be administered in the pediatric age group. Further studies are required to assess the therapeutic potential of citicoline in ADHD.

Recognan (citicoline) in the correction of asthenic and anxiety-depressive disorders

The article reflects the results of a number of studies that demonstrate the therapeutic effectiveness of Recognan (citicoline) in anxiety-depressive and asthenic disorders against the background of somatic and neurological diseases, in the correction of post-stroke depression. Recent experimental animal studies prove the effect of citicoline on anxiety and depression. In the complex effect, Recognan potentiates the main pharmacological effect of antidepressants and anxiolytics. In some studies, a dose-dependent change in animal behavior has been observed in response to the analgesic and antidepressant effects of citicoline. The effectiveness of citicoline in combination with transcranial direct current stimulation in the treatment of depression has been shown. The analysis of these research materials allows us to recommend Recognan in the complex therapy of asthenic and anxiety-depressive disorders in response to such pathological conditions as anxiety, asthenia, depression.

Efficacy of Citicoline Delivered via Brain Extracellular Space against Experimental Acute Ischemic Stroke in Rats.

Objective: Citicoline can be used to reduce acute ischemic stroke injury via venous infusion, however, its protective effects in the brain extracellular space remain largely unknown. Herein, we investigated the brain protective effects of citicoline administered via the brain extracellular space and sought precise effective dosage range that can protect against ischemic injury after experimental ischemic stroke in rats. Methods: Fifty-six Sprague-Dawley rats were randomly divided into control, intraperitoneal (IP), caudate-putamen (CPu)-25, CPu-40, CPu-50, CPu-60 and CPu-75 groups based on the infusion site and concentration of citicoline. Two hours after the administration of citicoline, the rats were subjected to a permanent middle cerebral artery occlusion to mimic acute ischemic stroke. Then, the brain infarct volume in rats after stroke was measured and their neurological deficiency was evaluated to explain the protective effects and effective dosage range of citicoline. Results: Compared to the control and IP groups, brain infarct volume of rats in CPu-40, CPu-50, and CPu-60 groups is significant smaller. Furthermore, the brain infarct volume of rats in CPu-50 is the least. Conclusions: Here, we showed that citicoline can decrease the brain infarct volume, thus protecting the brain from acute ischemic stroke injury. We also found that the appropriate effective citicoline dose delivered via the brain extracellular space is 50 mM. Our study provides novel insights into the precise treatment of acute ischemic stroke by citicoline via the brain extracellular space, further guiding the treatment of brain disease.

Citiholin u neurologiji i psihijatriji

Citicoline is a supplement-nootropic with potential applications in treating various neurological, psychiatric, and other conditions. There is experimental and clinical evidence of the benefits of citicoline in individuals after stroke, traumatic brain injury, and cognitive decline of various etiologies. Preclinical studies suggest that citicoline has neuroprotective and neurorestorative effects, which can be explained by its antioxidant, anti-inflammatory, and metabolic actions. Citicoline is necessary for the synthesis and stabilization of biological membranes, improves mitochondrial function, and is crucial in the synthesis of acetylcholine and other neurotransmitters in the central nervous system. No specific drugs are available for treating cognitive sequelae of stroke and traumatic brain injury. In experimental and clinical studies, citicoline has shown a safe profile with positive clinical effects on overall cognitive abilities, attention, executive function, and mood. There are also positive results of its use in patients with neurodegenerative diseases, although on a small number of participants. In psychiatry, the beneficial effects of citicoline on depression, negative symptoms of schizophrenia, and substance use disorders are described. This review provides an overview of the mechanisms of action of citicoline and summarizes the published research on its use in neurology and psychiatry.

Efek Terapi Citicoline terhadap Pemulihan Kognitif dan Motorik Pasien Stroke Iskemik Akut dengan Polimorfisme ApoE4 rs429358 dan rs7412

Citicoline has a neuroprotectant effect, especially in mild-to-moderate stroke. The presence of the ε4 allele in the ApoE gene is associated with a severe acute ischemic stroke (AIS) phenotype, in addition to neurodegenerative risk This study aims to determine the effect of citicoline on cognitive and motoric recovery in severe AIS biomolecularly, such as ApoE4 rs429358 and rs7412 polymorphisms. A 64-year-old woman was diagnosed with AIS with a 6-hour onset and with a NIHSS score of 25 and MMSE score of 21. The patient’s AIS was biomolecularly severe as proven by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) ApoE4 which yielded 482 bp at rs429358 (codon 112) and 249 bp 167 bp at rs7412 (codon 158) on electrophoretic visualization. The patient received 3x 500 mg intravenous citicoline for 4 days followed by another 1000 mg of citicoline intravenous during polyclinic control for 5 consecutive days. On the 9th day, the patient experienced improvement in cognitive function with an MMSE score of 29 and superior (4/5) and inferior (5/5) motoric strength. Citicoline is a neuroprotectant agent that is beneficial for the recovery of cognitive and motoric function in biomolecularly severe SIA (ApoE4, C/C, Arg112/Arg158) because it can save the penumbra area from infarction.

Chronic Disorders of Cerebral Circulation: a Challenge for the Family Doctor

The article examines modern views on the pathogenesis and clinical manifestations of chronic cerebral ischemia (CCI) and the possibilities of their pharmacotherapy. From this point of view, the requirements for choosing the optimal pharmacological strategy for pathological changes in the brain during ischemia are analyzed. The main goals of the clinical application of the strategy of neuroprotection in general, and in particular the need for a simultaneous effect on the neuronal, neurotransmitter and vascular mechanisms of the development of cognitive and general brain symptoms are considered. The necessity of using membrane-protective, cholinergic and vasotropic type of action is well founded. In this regard, the risks of polypharmacy in such patients and the arguments in favor of prescribing combined drugs were analyzed. The advantages of the innovative domestic combination containing citicoline and ginkgo biloba extract are considered in detail. The mechanisms of action and clinical effects of these components are analyzed with an emphasis on the prospects of their use in general medical practice. Special attention is paid to the justification of new opportunities provided by the synergistic effect of citicoline and ginkgo biloba extract when they are used in the form of a combined dosage form in comparison with monotherapy with these agents. The data on the safety of the use of the specified combination, as well as the scheme of dosage and course regimens, are given. The combination of citicoline + ginkgo biloba extract opens up new opportunities for family doctors in the pharmacotherapy of early cerebral vascular insufficiency symptoms.

Efficacy of citicoline as a supplement in glaucoma patients: A systematic review.

Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients. The present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool. Ten studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude. There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.

Effects of Citicoline and Atorvastatin Administration on the Regenerative Capacity of the Distal Segment of the Transected Sciatic Nerve in Conditions of Delayed Nerve Repair

Introduction: The reduced organ function following delayed nerve repair highlights the need for pharmacological interventions. In this regard, many chemical agents have been administered after nerve injury; however, their functional outcomes are not satisfying yet. The present study aimed to evaluate the effects of the administration of citicoline and atorvastatin on the regenerative capacity of the distal end of the transected sciatic nerve throughout a delayed nerve repair period. Method: The sciatic nerve of male rats (250-300 g) was transected, and the animals were intraperitoneally administrated citicoline (200 mg/kg, n=5), atorvastatin (5 mg/kg, n=5), citicoline + atorvastatin, and vehicles (control groups 1 and 2, n=5) for one month. In the sham group (n=5), the sciatic nerve was only exposed. After one month, the transected nerve was repaired. Fourteen weeks after surgical repair, morphometric and electron microscopic evaluations were performed on the nerve. Results: In the present study, improvement in the structural (fiber diameter, axon diameter, and myelin thickness, etc.) and ultrastructural (degree of myelin destruction) indices of the distal segment of the nerve was observed in the citicoline and atorvastatin groups compared to the control groups (P&lt; 0.01). In addition, the nerve structural and ultrastructural indices in the citicoline + atorvastatin group were better than each citicoline and atorvastatin group. Conclusion: The results of this study showed that the administration of citicoline and atorvastatin leads to maintaining the regeneration capacity of the distal part of the nerve in the condition of delayed nerve repair

Effect of citicoline and transcranial direct current stimulation on depressive-like behaviors in mice & quot

Recent investigations revealed the positive role of transcranial direct current stimulation (tDCS) in the treatment of depressive-like behavior & quot. Citicoline is a dietary supplement. It acts as a neuroprotective factor for the treatment of neurological disorders. The aim of this research was to evaluate a possible interaction between tDCS and citicoline on the modulation of depressive-like behavior s & quot in male mice. For tDCS, an electrode was surgically implanted in the left prefrontal of the brain of male mice & quot. Acute restraint stress was induced by movement restraint for 4 h. Locomotor activity and depressive-like behaviors & quot were examined by open field test (OFT), forced swimming test (FST), and tail suspension test (TST). The results indicated that the intraperitoneal (i.p.) administration of citicoline, left prefrontal anodal tDCS, and co-treatment of citicoline and tDCS had no significant effect on locomotor activity. I.p. injection of citicoline (30 mg/kg) decreased immobility time in the FST and TST, showing an antidepressant-like effect & quot. Moreover, the application of left prefrontal anodal tDCS (0.2 mA) for 20 min induced antidepressant-like effect & quot by reducing immobility time in the FST and TST. Co-administration of citicoline (7 and 15 mg/kg) along with tDCS (0.1 mA) decreased immobility time in the FST and TST, indicating an antidepressant-like effect & quot. Therefore, it can be concluded that administration of citicoline in combination with tDCS enhanced the efficacy of tDCS for remedy of depressive-like behaviors & quot.