Cytidine does not affect acute toxicity of intravenously administered choline.

Cytidine-5'-diphosphocholine (CDP-choline) is a key precursor for the intracellular synthesis of phosphatidylcholine and other phospholipids. Following either intravenous or oral application citicoline (CDP-choline of exogenous origin) undergoes quick decomposition to cytidine and choline, and for this reason it is frequently considered a prodrug. However, upon acute intravenous application in mice citicoline is, on a molar basis, 20 times less toxic than choline. To find out whether cytidine may attenuate toxicity of choline, in the present experiments we compared maximum tolerated doses of single intravenous injections of choline and equimolar mixture of choline and cytidine. We assumed that, if after oral intake a substantial part of citicoline is catabolised already in the intestine and its catabolites enter blood separately, intravenously applied equimolar mixture of cytidine and choline will be markedly less toxic than an equivalent molar dose of choline. However, the maximum tolerated single doses determined in our experiment for choline and equimolar mixture of choline and cytidine were similar. These data suggest that citicoline taken orally is not significantly decomposed in the intestinal lumen, but absorbed to blood as the intact molecule.

Dysregulation of choline metabolism and therapeutic potential of citicoline in Huntington's disease.

Huntington's disease (HD) is associated with dysregulated choline metabolism, but the underlying mechanisms remain unclear. This study investigated the expression of key enzymes in this pathway in R6/2 HD mice and human HD postmortem brain tissues. We further explored the therapeutic potential of modulating choline metabolism for HD. Both R6/2 mice and HD patients exhibited reduced expression of glycerophosphocholine phosphodiesterase 1 (GPCPD1), a key enzyme in choline metabolism, in the striatum and cortex. The striatum of R6/2 mice also showed decreased choline and phosphorylcholine, and increased glycerophosphocholine, suggesting disruption in choline metabolism due to GPCPD1 deficiency. Treatment with citicoline significantly improved motor performance, upregulated anti-apoptotic Bcl2 expression, and reduced oxidative stress marker malondialdehyde in both brain regions. Metabolomic analysis revealed partial restoration of disrupted metabolic patterns in the striatum and cortex following citicoline treatment. These findings strongly suggest the role of GPCPD1 deficiency in choline metabolism dysregulation in HD. The therapeutic potential of citicoline in R6/2 mice highlights the choline metabolic pathway as a promising target for future HD therapies.

Current neuroprotective agents in stroke.

What is expected from neuroprotection is to inhibit neuronal death and halt or decelerate the neuronal loss to lower the mortality rates, decrease disability, and improve the quality of life following an acute ischemic stroke. Several agents were described as neuroprotective up to date; however, there is still debate which to use in the neurorehabilitation of stroke patients, in terms of both efficacy and also safety. In this review, we discuss the agents, citicoline, cerebrolysin and MLC901 (NeuroAiD II), the three agents which have started to be used frequently in neurorehabilitation clinics recently in the light of the current literature.

'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 additive effect between bupropion and citicoline upon induction of anti-nociceptive effect in nerve-ligated mice.

OBJECTIVES: Bupropion is an atypical antidepressant that shows robust efficacy in the regulation of neuropathic pain. Citicoline is a dietary supplement which is used as a neuroprotective agent for central nervous system (CNS) disorders. The probable interaction between bupropion and citicoline on neuropathic pain was assessed in male mice. METHODS: Neuropathic pain was induced by sciatic nerve ligation. Neuropathic pain was examined in nerve-ligated mice using tail-flick and hot-plate tests. RESULTS: The results indicated that intraperitoneal (i.p.) administration of citicoline (50 and 100 mg/kg) induced an anti-nociceptive effect in nerve-ligated animals. Similarly, i.p. injection of bupropion (2.5 and 5 mg/kg) induced anti-nociceptive effects in nerve-ligated mice. Co-administration of different doses of bupropion (2.5 and 5 mg/kg) along with a low dose of citicoline (25 mg/kg) caused an anti-nociceptive effect by enhancement of tail-flick and hot plate latencies. Interestingly, there is an additive effect between bupropion and citicoline upon the induction of the anti-nociceptive effect. CONCLUSIONS: Based on these results, it can be concluded that there is an interaction between bupropion and citicoline upon induction of an anti-nociceptive effect in nerve-ligated mice.

[Recognan (citicoline) in the correction of asthenic and anxiety-depressive disorders]. / Rekognan (tsitikolin) v korrektsii astenicheskikh i trevozhno-depressivnykh narushenii.

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.

Citicoline modulates inflammatory signaling pathways in the spleen of rats exposed to gamma-radiation.

BACKGROUND AND AIM: The spleen has an essential role in immune responses regulation and is considered the biggest peripheral immune organ. Citicoline is used for various brain disorders management. This study aimed to examine the using possibility of citicoline to treat γ-radiation-induced splenic inflammation in rats. MATERIALS AND METHODS: Eighteen male albino rats were classified into: Group 1 (control) animals were kept as control. Group 2 (γ-radiation) animals were total-body γ-irradiated with 6 Gy. Group 3 (γ-radiation + citicoline) rats were γ-irradiated with 6 Gy, then injected intraperitoneally with citicoline (300 mg/kg/d) 5 min after irradiation for one week. Levels of TNF-α, IL-1ß, iNOS, NF-κB, JAK2, and STAT3 were determined in spleen tissue, along with histopathological examination. RESULTS: Rats exposure to gamma-radiation led to elevation in splenic TNF-α, IL-1ß, NF-κB, iNOS, JAK2, and STAT3 levels significantly. Treatment with citicoline after gamma-radiation exposure improved this elevation, and modulated gamma-radiation-induced histopathological alterations. CONCLUSIONS: This data showed that citicoline inhibited γ-radiation-induced splenic inflammation via suppressing NF-κB and JAK2/STAT3 signaling pathways in spleen tissue.

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

Background: Citicoline is a naturally occurring compound with pleiotropic effects on neuronal function and cognitive processes. Objective: 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. Methods: 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). Results: A significant difference in MMSE score was found in the average between the two groups of treatment at 6 and 12 months. Conclusions: 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.

SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure.

BACKGROUND: The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses. METHODS: We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined. DISCUSSION: Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients. TRIAL REGISTRATION: The trial was registered at www. CLINICALTRIALS: gov on 5/31/2023 (NCT05881135). TRIAL STATUS: Currently enrolling.

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.

Neuroprotection by Cerebrolysin and Citicoline Through the Upregulation of Brain-Derived Neurotrophic Factor (BDNF) Expression in the Affected Neural Cells: A Preliminary Clue Obtained Through an In Vitro Study.

OBJECTIVES: Citicoline and cerebrolysin are two unique yet contentious medications because of inconsistencies in efficacy as well as the mystery surrounding their mode of action. The current study aimed to re-validate the neuroprotective benefits of these medications and investigate the possible molecular mechanism. METHODS: Neuro-2A cells were exposed to tert-butyl hydroperoxide, a consistent in vitro model of neuronal damage caused by oxidative stress. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, acridine orange/ethidium bromide (AO-EtBr) staining, and phase-view examinations were utilized to evaluate cell survival and cytotoxicity. Real-time reverse transcription-polymerase chain reaction (RT-PCR)-based gene expression studies were conducted. KEY FINDING: Observations revealed that these two medications had modest but considerable neuroprotective effects. While the majority of the genes' expressions remained unchanged, cerebrolysin upregulated Neuregulin 1, and both upregulated brain-derived neurotrophic factor (BDNF) expression. CONCLUSION: The findings of the current study may be the first to suggest that citicoline and cerebrolysin may increase host cells' defense mechanisms (secretion neurotrophic factors) rather than carrying nutrients for cell survival. Because of its simplicity, the current study can readily be repeated to learn more about these two disputed medications for treating ischemic stroke.

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). METHOD: Mice 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. RESULTS: In 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. CONCLUSION: The combination synergistically improved emotion-like behaviors, alleviating the inflammation and upregulating the hippocampal BDNF-mediated CREB signaling pathway.

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.

[Asthenic disorders correction with Recognan]. / Korrektsiya astenicheskikh sostoyanii preparatom Rekognan.

Asthenia, asthenic syndrome, asthenic condition, asthenic reaction, asthenic disorders are terms that describe the state of «impotence¼. Fatigue that occurs against the background of habitual physical or intellectual stress for a person, and persists after rest, is asthenia. For people of the older age group, the term senile asthenia syndrome is used. Asthenia manifests itself with increased fatigue and exhaustion, mood instability, increased irritability, sleep disorders. Asthenic conditions manifest themselves along with a decrease in physical activity, increased cognitive and mental fatigue. Asthenic syndrome (AS) are considered as an integral part of cardiovascular diseases (CVD), as one of the manifestations of cerebrovascular pathology. Senile asthenia syndrome (SAS) is a geriatric syndrome characterized by an age-associated decrease in the physiological reserve and functions of many body systems, including cognitive functions. One of the drugs that has a positive effect on the severity of AS and improves the state of cognitive functions is the domestic drug Recognan (citicoline). The effectiveness of Recognan in the treatment of AS in patients with CVD, SAS, and post-COVID asthenia has been shown. It is recommended to prescribe Recognan orally at 500 mg / day for 30 days. Recognan has a nootropic and antiasthenic effect.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results suggested an interaction between citicoline and cannabinoid CB1 receptors on the modulation of depression-like behaviors in the NARS and ARS mice.

Memory Recovery Effect of a New Bioactive Innovative Combination in Rats with Experimental Dementia.

Alzheimer's disease manifests as a complex pathological condition, with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease, current therapeutic strategies aim at a multitargeted approach, often relying on a combination of substances with versatile and complementary effects. In the present study, a unique combination of α-lipoic acid, citicoline, extracts of leaves from olive tree and green tea, vitamin D3, selenium and an immune-supporting complex was tested in scopolamine-induced dementia in rats. Using behavioral and biochemical methods, we assessed the effects of the combination on learning and memory, and elucidated the mechanisms of these effects. Our results showed that, compared to its components, the experimental combination was most efficient in improving short- and long-term memory as assessed by the step-through method as well as spatial memory as assessed by T-maze and Barnes maze underlined by decreases in AChE activity (p < 0.05) and LPO (p < 0.001), increases in SOD activity in the cortex (p < 0.05) and increases in catalase (p < 0.05) and GPx (p < 0.01) activities and BDNF (p < 0.001) and pCREB (p < 0.05) levels in the hippocampus. No significant histopathological changes or blood parameter changes were detected, making the experimental combination an effective and safe candidate in a multitargeted treatment of AD.

Citicolina, ¿deberíamos seguir indicándola en ECV isquémica? / Citicolina, devemos continuar a indicá-lo nA DCbV isquemica? / Citicoline, should we continue to indicate it in ischemic CVD?

Resumen: La enfermedad cerebrovascular (ECV) isquémica es una condición médica que implica, según su grado, discapacidad importante para el paciente, además de altos costos para su tratamiento agudo y crónico, así como en el manejo de la discapacidad con alta incidencia y prevalencia a nivel mundial. Desde el punto de vista fisiopatológico, representa una catástrofe en el funcionamiento cerebral que involucra daño estructural y funcional. Se han desarrollado múltiples estrategias para el manejo de esta patología; actualmente, el estándar de oro para su manejo es el rt-PA; sin embargo, por sus características, pocos pacientes tienen acceso al mismo. Razón por la que se han desarrollado estrategias farmacológicas diversas para su manejo: la citicolina se ha usado durante años, no obstante, genera controversias dado que su utilidad, demostrada en estudios experimentales, no se ha reproducido en la práctica clínica; más aún, algunos estudios sugieren que podría empeorar el pronóstico del paciente, lo que justificaría el abandono de su uso en el tratamiento de ECV isquémica (ictus). Por tal motivo ofrecemos esta revisión del tema con el fin de brindar herramientas que permitan aclarar dicha controversia.

Abstract: Ischemic cerebrovascular disease (CVD) is a medical condition that, according to its extension, implies significant disability for the patient, as well as high costs for its acute and chronic treatment, as well in the management of disability, with high incidence and worldwide prevalence, from the physiopathological point of view represents a catastrophe in brain functioning that involves structural and functional damage. Multiple strategies have been developed for the management of this pathology, currently the gold standard for its management is the rt-PA, however, due to its characteristics, and few patients have access to it, because it various pharmacological strategies have been developed. Citicoline has been used for years, nevertheless generates controversies since its usefulness, demonstrated in experimental studies, has not been reproduced in clinical practice but some studies suggest that it could worsen the patient's prognosis, which would justify the abandonment of its use in the treatment of ischemic CVD (ictus), for this reason we offer this review of the subject in order to provide tools to clarify this controversy.

Resumo: A doença cerebrovascular (DCbV) isquêmica é uma condição clínica que de acordo com sua extensão, implica em uma significativa incapacidade para o paciente, ademais de altos custos para seu tratamento agudo e crônico, bem como no manejo da incapacidade com alta incidência e prevalência a nível mundial. Do ponto de vista fisiopatológico representa uma catástrofe no funcionamento do cérebro que envolve danos estruturais e funcionais. Múltiplas estratégias têm sido desenvolvidas para o tratamento dessa patologia, atualmente o padrão ouro para o seu manejo é o rt-PA, porém, devido às suas características, poucos pacientes têm acesso a ele, razão pela qual várias estratégias farmacológicas foram desenvolvidas, a citicolina vem sendo utilizada há anos, gera controvérsias, uma vez que sua utilidade, demonstrada em estudos experimentais não foi reproduzida na prática clínica, mas alguns estudos sugerem que ela poderia piorar o prognóstico do paciente, o que justificaria o abandono do seu uso no tratamento de DCbV isquêmica (ictus), por esse motivo oferecemos esta revisão, a fim de fornecer ferramentas para esclarecer esta controvérsia.