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.

EFFECT OF INVESTIGATIONAL COMBINATIONS OF NEUROPROTECTANTS ON THE LEVEL OF S 100 AND NSE PROTEIN IN THE BLOOD SERUM OF PATIENTS WITH MODERATE AND SEVERE ISCHEMIC STROKE.

Ischemic cerebral stroke (ICS) is a devastating neurological pathology associated with enormous comorbidity and mortality. Preliminary experimental screening of cerebroprotective agents with different mechanisms of action was performed: Edaravone, Cerebrolysin, Choline alfoscerate, Citicoline, Mexidol, the most effective combinations of cerebroprotectors were identified, followed by their screening for efficacy in clinical conditions by neuron-specific enolase (NSE) and S100 protein, as one of the main biochemical markers of brain damage in acute ischemic stroke. Different combinations of neuroprotectants identified as the most effective in experimental screening differed in their ability to correct serum levels of S100 and NSE protein in ischemic stroke in clinical settings. The lowest effectiveness in the correction of neuroglioproliferative processes was recorded when using only conventional therapy (CT), which was determined according to the Order of the Ministry of Health of Ukraine of 03.08.2012 №602, without the use of neuroprotectors. Whereas, the use of a neuroprotective combination/complex (NPC) (cerebrolysin+citicoline) in the treatment of ischemic strokes in terms of the effectiveness of correction of neuroglioproliferative processes was 1,7-2,7 times (p<0.01) higher than conventional therapy, and 1,2-1,4 times (p<0.05) higher than treatment that included the use of a neuroprotective combination - cerebrolysin+mexidol.

CDP-choline modulates cholinergic signaling and gut microbiota to alleviate DSS-induced inflammatory bowel disease.

Inflammatory bowel diseases (IBD) represent chronic gastrointestinal inflammatory disorders characterized by a complex and underexplored pathogenic mechanism. Previous research has revealed that IBD patients often have a deficiency of choline and its metabolites, including acetylcholine (ACh) and phosphatidylcholine (PC), within the colon. However, a comprehensive study linking these three substances and their mechanistic implications in IBD remains lacking. This study aimed to investigate the efficacy and underlying mechanism of cytidine diphosphate (CDP)-choline (citicoline), an intermediate product of choline metabolism, in a mouse model of IBD induced by dextran sulfate sodium salt (DSS). The results demonstrated that CDP-choline effectively alleviated colonic inflammation and deficiencies in choline, ACh, and PC by increasing the raw material. Further detection showed that CDP-choline also increased the ACh content by altering the expression of high-affinity choline transporter (ChT1) and acetylcholinesterase (AChE) in DSS-induced mice colon. Moreover, CDP-choline increased the expression of alpha7 nicotinic acetylcholine receptor (α7 nAChR) and activated the cholinergic anti-inflammatory pathway (CAP), leading to reduced colon macrophage activation and proinflammatory M1 polarization in IBD mice, thus reducing the levels of TNF-α and IL-6. In addition, CDP-choline reduced intestinal ecological imbalance and increased the content of hexanoic acid in short-chain fatty acids (SCFAs) in mice. In conclusion, this study elucidates the ability of CDP-choline to mitigate DSS-induced colon inflammation by addressing choline and its metabolites deficiencies, activating the CAP, and regulating the composition of the intestinal microbiome and SCFAs content, providing a potential prophylactic and therapeutic approach for IBD.

The Combination of Citicoline and Nicotinamide Mononucleotide Induces Neurite Outgrowth and Mitigates Vascular Cognitive Impairment via SIRT1/CREB Pathway.

Vascular dementia (VD) is characterized with vascular cognitive impairment (VCI), which currently has few effective therapies in clinic. Neuronal damage and white matter injury are involved in the pathogenesis of VCI. Citicoline has been demonstrated to exhibit neuroprotection and neurorepair to improve cognition in cerebrovascular diseases. Nicotinamide adenine dinucleotide (NAD+)-dependent sirtuin (SIRT) signaling pathway constitutes a strong intrinsic defense system against various stresses including neuroinflammation in VCI. Our hypothesis is that the combined use of citicoline and the precursor of NAD+, nicotinamide mononucleotide (NMN), could enhance action on cognitive function in VCI. We investigated the synergistic effect of these two drugs in the rat model of VCI by bilateral common carotid artery occlusion (BCCAO). Citicoline significantly enhanced neurite outgrowth in Neuro-2a cells, and the combination of citicoline and NMN remarkably induced neurite outgrowth in Neuro-2a cells and primary cortical neuronal cells with an optimal proportion of 4:1. In the rat model of BCCAO, when two drugs in combination of 160 mg/kg citicoline and 40 mg/kg NMN, this combination administrated at 7 days post-BCCAO significantly improved the cognitive impairment in BCCAO rats compared with vehicle group by the analysis of the Morris water maze and the novel object recognition test. This combination also decreased microglial activation and neuroinflammation, and protected white matter integrity indicated by the increased myelin basic protein (MBP) expression through activation of SIRT1/TORC1/CREB signaling pathway. Our results suggest that the combination of citicoline and NMN has a synergistic effect for the treatment of VD associated with VCI.

The effect of nicotine on antidepressant and anxiolytic responses induced by citalopram and citicoline in mice.

The effect of nicotine on both anxiety and depression has been broadly studied. Moreover, citalopram and citicoline play a role in the modulation of anxiety and depression. This study was designed to examine the effects of nicotine on the antidepressant and anxiolytic responses induced by citalopram and citicoline in mice. Anxiety­ and depression­related behaviors were assessed with the elevated plus maze and forced swim test, respectively. The results showed that subcutaneous administration of nicotine decreased open­arm time (OAT) and open­arm entries (OAE) but increased immobility time, suggesting anxiogenic­like and depressive­like effects. Intraperitoneal administration of citalopram increased OAT but decreased immobility time, indicating that citalopram induced anxiolytic­like and antidepressant­like responses. Additionally, an injection of citicoline increased OAE but decreased immobility time, revealing anxiolytic­like and antidepressant­like effects. Interestingly, the subthreshold dose of nicotine potentiated the citalopram and citicoline effects on OAT and immobility time, which revealed anxiolytic­like and antidepressant­like behaviors. Locomotor activity was not significantly changed by any doses of the drugs. In conclusion, these findings suggest that interactions between nicotine and citalopram or citicoline occur upon induction of anxiolytic and antidepressant responses in mice.

The Role of P2Y6 Receptors in the Mechanisms of the Neuroprotective Effect of Citicoline.

Spontaneous bioelectrical activity of the brain and the duration of gasping were recorded in mice during modeling of global strangulation ischemia of the brain against the background of preventive administration of citicoline. The maximum neuroprotective effect of citicoline was observed when it was administered 60 min before the simulation of ischemia and was completely prevented by preliminary administration of a selective P2Y6 receptor antagonist MRS2578. The obtained experimental data attest to the leading role of receptor mechanisms in the implementation of neuroprotective activity of citicoline.

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.

An α7 nAChR approach for the baseline-dependent modulation of deviance detection in schizophrenia: A pilot study assessing the combined effect of CDP-choline and galantamine.

BACKGROUND: Cognitive operations including pre-attentive sensory processing are markedly impaired in patients with schizophrenia (SCZ) but evidence significant interindividual heterogeneity, which moderates treatment response with nicotinic acetylcholine receptor (nAChR) agonists. Previous studies in healthy volunteers have shown baseline-dependency effects of the α7 nAChR agonist cytidine 5'-diphosphocholine (CDP-choline) administered alone and in combination with a nicotinic allosteric modulator (galantamine) on auditory deviance detection measured with the mismatch negativity (MMN) event-related potential (ERP). AIM: The objective of this pilot study was to assess the acute effect of this combined α7 nAChR-targeted treatment (CDP-choline/galantamine) on speech MMN in patients with SCZ (N = 24) stratified by baseline MMN responses into low, medium, and high baseline auditory deviance detection subgroups. METHODS: Patients with a stable diagnosis of SCZ attended two randomized, double-blind, placebo-controlled and counter-balanced testing sessions where they received a placebo or a CDP-choline (500 mg) and galantamine (16 mg) treatment. MMN ERPs were recorded during the presentation of a fast multi-feature speech MMN paradigm including five speech deviants. Clinical measures were acquired before and after treatment administration. RESULTS: While no main treatment effect was observed, CDP-choline/galantamine significantly increased MMN amplitudes to frequency, duration, and vowel speech deviants in low group individuals. Individuals with higher positive and negative symptom scale negative, general, and total scores expressed the greatest MMN amplitude improvement following CDP-choline/galantamine. CONCLUSIONS: These baseline-dependent nicotinic effects on early auditory information processing warrant different dosage and repeated administration assessments in patients with low baseline deviance detection levels.

The Role of Citicoline and Coenzyme Q10 in Retinal Pathology.

Ocular neurodegenerative diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration are common retinal diseases responsible for most of the blindness causes in the working-age and elderly populations in developed countries. Many of the current treatments used in these pathologies fail to stop or slow the progression of the disease. Therefore, other types of treatments with neuroprotective characteristics may be necessary to allow a more satisfactory management of the disease. Citicoline and coenzyme Q10 are molecules that have neuroprotective, antioxidant, and anti-inflammatory properties, and their use could have a beneficial effect in ocular neurodegenerative pathologies. This review provides a compilation, mainly from the last 10 years, of the main studies that have been published on the use of these drugs in these neurodegenerative diseases of the retina, analyzing the usefulness of these drugs in these pathologies.

Is Citicoline Effective in Preventing and Slowing Down Dementia?-A Systematic Review and a Meta-Analysis.

BACKGROUND: Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment. Nutritional supplements have been extensively investigated, and citicoline seems to be a promising agent; its role in clinical practice, however, has not been established. We systematically reviewed studies on the effect of citicoline on cognitive performance. METHODS: We searched the PubMed and Cochrane Library databases for articles published between 2010 and 2022. Relevant information was extracted and presented following the PRISMA recommendations. Data were pooled using the inverse-variance method with random effects models. RESULTS: We selected seven studies including patients with mild cognitive impairment, Alzheimer's disease or post-stroke dementia. All the studies showed a positive effect of citicoline on cognitive functions. Six studies could be included in the meta-analysis. Overall, citicoline improved cognitive status, with pooled standardized mean differences ranging from 0.56 (95% CI: 0.37-0.75) to 1.57 (95% CI: 0.77-2.37) in different sensitivity analyses. The overall quality of the studies was poor. DISCUSSION: Available data indicate that citicoline has positive effects on cognitive function. The general quality of the studies, however, is poor with significant risk of bias in favor of the intervention. Other: PubMed and the Cochrane Library.

Choline and citicoline ameliorate oxidative stress in acute kidney injury in rats.

OBJECTIVES: The purpose of this study is to investigate the effects of cholinergic anti-inflammatory pathway (CAP)-activating drugs, choline and citicoline (Cytidinediphosphate-choline, CDP-choline), on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) parameters and the contribution of NADPH Oxidase4 (NOX4) p22phox. BACKGROUND: Endotoxemia induces a systemic inflammatory response characterized by the production of pro-inflammatory mediators and reactive oxygen species (ROS), which eventually develops acute kidney injury (AKI). NADPH Oxidase4 (NOX4) p22phox pathway contributes to the development of endotoxemia-induced AKI. Inflammatory response can be controlled by CAP. METHODS: Expressions levels of KIM-1, TNF-α, NOX4, p22phox and NFκB in the kidney tissues of rats were analyzed via RT-PCR in experimental groups; 1. Control, 2. LPS (10 mg/kg) + saline, 3. LPS + CDP-choline (375 mg/kg) and 4. LPS + choline (90 mg/kg). Choline and ROS levels in kidney tissues were also measured by a spectrofluorometric assay. RESULTS: LPS-induced elevations of ROS levels were decreased by CDP-choline or choline administration (p < 0.001). LPS-elevated KIM-1, TNFα, NOX4, p22 phox, and NFκB expressions were significantly decreased by choline or CDP-choline treatments (p < 0.001). CONCLUSION: Decreased ROS production in kidney tissues in treatment groups suggests that choline or CDP-choline may have therapeutic potential in endotoxemia-associated AKI via downregulating NOX4 and p22phox expressions (Tab. 1, Fig. 5, Ref. 45). Text in PDF www.elis.sk Keywords: endotoxemia, choline, cytidine diphosphate choline, acute kidney injury, reactive oxygen species.

Preventive effects of antenatal CDP-choline in a rat model of neonatal hyperoxia-induced lung injury.

Antenatal steroid administration to pregnant women at risk of prematurity provides pulmonary maturation in infants, while it has limited effects on incidence of bronchopulmonary dysplasia (BPD), the clinical expression of hyperoxia-induced lung injury (HILI). Cytidine-5'-diphosphate choline (CDP-choline) was shown to alleviate HILI when administered to newborn rats. Therefore, we investigated effects of maternal administration of CDP-choline, alone or in combination with betamethasone, on lung maturation in neonatal rats subjected to HILI immediately after birth. Pregnant rats were randomly assigned to one of the four treatments: saline (1 mL/kg), CDP-choline (300 mg/kg), betamethasone (0.4 mg/kg), or CDP-choline plus betamethasone (combination therapy). From postnatal day 1 to 11, pups born to mothers in the same treatment group were pooled and randomly assigned to either normoxia or hyperoxia group. Biochemical an d histopathological effects of CDP-choline on neonatal lung tissue were evaluated. Antenatal CDP-choline treatment increased levels of phosphatidylcholine and total lung phospholipids, decreased apoptosis, and improved alveolarization. The outcomes were further improved with combination therapy compared to the administration of CDP-choline or betamethasone alone. These results demonstrate that antenatal CDP-choline treatment provides benefit in experimental HILI either alone or more intensively when administered along with a steroid, suggesting a possible utility for CDP-choline against BPD.

Citicoline: pharmacological and clinical review, 2022 update. / Citicolina: revisión farmacológica y clínica, actualización 2022.

This review is based on the previous one published in 2016 (Secades JJ. Citicoline: pharmacological and clinical review, 2016 update. Rev Neurol 2016; 63 (Supl 3): S1-S73), incorporating 176 new references, having all the information available in the same document to facilitate the access to the information in one document. This review is focused on the main indications of the drug, as acute stroke and its sequelae, including the cognitive impairment, and traumatic brain injury and its sequelae. There are retrieved the most important experimental and clinical data in both indications.

TITLE: Citicolina: revisión farmacológica y clínica, actualización 2022.Esta revisión se basa en la publicada en 2016 ­Secades JJ. Citicolina: revisión farmacológica y clínica, actualización 2016. Rev Neurol 2016; 63 (Supl 3): S1-S73­, e incorpora 176 nuevas referencias aparecidas desde entonces, con toda la información disponible para facilitar el acceso a toda la información en un único documento. La revisión se centra en las principales indicaciones del fármaco, como los accidentes cerebrovasculares agudos y sus secuelas, incluyendo el deterioro cognitivo, y los traumatismos craneoencefálicos y sus secuelas. Se recogen los principales aspectos experimentales y clínicos en estas indicaciones.

Brain Targeting of Citicoline Sodium via Hyaluronic Acid-Decorated Novel Nano-Transbilosomes for Mitigation of Alzheimer's Disease in a Rat Model: Formulation, Optimization, in vitro and in vivo Assessment.

Background: Alzheimer's disease (AD) is one of the furthermost advanced neurodegenerative disorders resulting in cognitive and behavioral impairment. Citicoline sodium (CIT) boosts the brain's secretion of acetylcholine, which aids in membrane regeneration and repair. However, it suffers from poor blood-brain barrier (BBB) permeation, which results in lower levels of CIT in the brain. Purpose: This study targeted to encapsulate CIT into novel nano-platform transbilosomes decorated with hyaluronic acid CIT-HA*TBLs to achieve enhanced drug delivery from the nose to the brain. Methods: A method of thin-film hydration was utilized to prepare different formulae of CIT-TBLs using the Box-Behnken design. The optimized formula was then hyuloranated via integration of HA to form the CIT-HA*TBLs formula. Furthermore, AD induction was performed by aluminum chloride (Alcl3), animals were allocated, and brain hippocampus tissue was isolated for ELISA and qRT-PCR analysis of malondialdehyde (MDA), nuclear factor kappa B (NF-kB), and microRNA-137 (miR-137) coupled with immunohistochemical amyloid-beta (Aß1-42) expression and histopathological finding. Results: The hyuloranated CIT-HA*TBLs formula, which contained the following ingredients: PL (300 mg), Sp 60 (43.97 mg), and SDC (20 mg). They produced spherical droplets at the nanoscale (178.94 ±12.4 nm), had a high entrapment efficiency with 74.92± 5.54%, had a sustained release profile of CIT with 81.27 ±3.8% release, and had ex vivo permeation of CIT with 512.43±19.58 µg/cm2. In vivo tests showed that CIT-HA*TBL thermogel dramatically reduces the hippocampus expression of miR-137 and (Aß1-42) expression, boosting cholinergic neurotransmission and decreasing MDA and NF-kB production. Furthermore, CIT-HA*TBLs thermogel mitigate histopathological damage in compared to the other groups. Conclusion: Succinctly, the innovative loading of CIT-HA*TBLs thermogel is a prospectively invaluable intranasal drug delivery system that can raise the efficacy of CIT in Alzheimer's management.

Morphological investigation of protective effects of CDP-choline on liver and small intestine in an experimental sepsis model in rats / Investigación morfológica de los efectos protectores de la CDP-colina en el hígado y el intestino delgado en un modelo experimental de sepsis en ratas

SUMMARY: Fifty male Wistar albino rats were divided into 5 groups; Group 1 as a sham group. Group 2 as a control group, Group 3 as 100 mg/kg CDP-choline administered group, Group as 200 mg/kg CDP-choline administered group, and Group 5 as sepsis group. The sepsis model was performed by ligating and perforating the caecum of rats. Liver and small intestine tissues were assessed either histologically or quantitatively and qualitatively. There was a significant difference between the sepsis and CDP-choline groups for liver and intestinal damage evaluated in tissue samples. (p <0.001). CDP-choline treatment partially improved dose-dependent the clinical parameters of sepsis and septic shock, reversed micro-anatomical damage caused by sepsis.

Cincuenta ratas albinas Wistar macho se dividieron en 5 grupos; Grupo 1 como grupo control simulador, el grupo 2 como grupo de control, el grupo 3 como grupo al que se administró 100 mg/kg de CDP-colina, el grupo 4 como grupo al que se administró 200 mg/kg de CDP-colina y el grupo 5 como grupo con sepsis. El modelo de sepsis se realizó ligando y perforando el intestino ciego de las ratas. Los tejidos del hígado y del intestino delgado se evaluaron histológicamente o cuantitativa y cualitativamente. Hubo una diferencia significativa entre los grupos de sepsis y CDP-colina para el daño hepático e intestinal evaluado en muestras de tejido (p<0,001). El tratamiento con CDP-colina mejoró parcialmente, según la dosis, los parámetros clínicos de sepsis y shock séptico y revirtió el daño micro anatómico causado por la sepsis.

Citicoline Eye Drops Protect Trabecular Meshwork Cells from Oxidative Stress Injury in a 3D In Vitro Glaucoma Model.

Intraocular pressure (IOP) is considered an important modifiable risk factor for glaucoma, which is known as the second leading cause of blindness worldwide. However, lowering the IOP is not always sufficient to preserve vision due to other non-IOP-dependent mechanisms being involved. To improve outcomes, adjunctive therapies with IOP-independent targets are required. To date, no studies have shown the effect of citicoline on the trabecular meshwork (TM), even though it is known to possess neuroprotective/enhancement properties and multifactorial mechanisms of action. Given that reactive oxygen species seem to be involved in glaucomatous cascade, in this present study, an advanced millifluidic in vitro model was used to evaluate if citicoline could exert a valid TM protection against oxidative stress. To this end, the cellular behavior, in terms of viability, apoptosis, mitochondrial state, senescence and pro-inflammatory cytokines, on 3D human TM cells, treated either with H2O2 alone or cotreated with citicoline, was analyzed. Our preliminary in vitro results suggest a counteracting effect of citicoline eye drops against oxidative stress on TM cells, though further studies are necessary to explore citicoline's potential as a TM-target therapy.

The Effect of Citicoline on Ethambutol Optic Neuropathy: Histopathology and Immunohistochemistry Analysis of Retina Ganglion Cell Damage Level in Rat Model.

Purpose: Ethambutol therapy in certain doses and period can cause bilateral ocular intoxication. There is no definitive therapy that has been found to prevent damage to retina neuronal cells in ethambutol optic neuropathy (EON) cases. Citicoline is thought to have a potential effect to maintain retinal neuron cells. This study aimed to analyze the effect of citicoline on damaged rat ganglion cells in EON. Methods: An experimental study of 15 Wistar rats was divided into 3 groups: the nontreatment group (A), the ethambutol (35 mg/kg/day) group (B), and the ethambutol (35 mg/kg/day) and citicoline (1 g/kg/day) group (C). Groups B and C were given treatment orally for 30 days, then a histopathology examination was performed to analyze retinal ganglion cell (RGC) density, and immunohistochemistry to assess bcl-2 and caspase-3 expression. Results: RGC density of rat with ethambutol intoxication that received citicoline was higher than those who did not get citicoline (P < 0.001). The rat retina ganglion layer without citicoline administration is thicker than the one with citicoline, the increase in thickness is due to the formation of vacuoles in the cytoplasm of ganglion cells. Rat with citicoline obtained higher bcl-2 ganglion expression, and lower caspase-3 expression compared with rat without citicoline. Conclusions: The ganglion cells damage process caused by EON can be suppressed by citicoline administration. It was proven by analyzing RGC density, ganglion layer thickness, and expression level of bcl-2 and caspase-3 on rat model.

Nonlinear surface EMG analysis to detect the neuroprotective effect of citicoline in rat sciatic nerve crush injury.

Surface electromyography (sEMG) is a method involving physiological signals with a complex behavior. The aim is to analyze the sEMG signals by nonlinear techniques for investigating the possible neuroprotective effect of citicoline for early period of administration in rat sciatic nerve crush injury. Thirty-two Wistar rats were randomized into four groups: the sham-operated group with the intact sciatic nerve and the sciatic nerve crush groups, which received crush on the left sciatic nerve and administrated i.p. citicoline (50 and 250 mg/kg/day, 7 day) or saline (control group). Function assessment analysis was performed and sEMG signals were recorded and analyzed with nonlinear methods. Citicoline administration improved functional recovery in comparison with control group. Largest Lyapunov exponent and correlation dimension parameters were decreased due to the crush injury and increased related with the healing of sciatic nerve. Results of nonlinear analysis of sEMG are in line with the results of functional recovery and electrophysiological assessments. These results suggest that administration of citicoline protects the sciatic nerve from the crush injury which may be attributed to its antioxidative properties. Nonlinear analysis of sEMG is a promising supporting method for determining the nerve regeneration process during the treatment of peripheral nerve injuries.

Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress.

BACKGROUND: The present study aimed to investigate the rationale and efficacy of using a citicoline, coenzyme Q10 (CAVAQ10) and vitamin B3 fixed combination in combating inflammation and oxidation in neuronal cells exposed to oxidative stress. METHODS: HypoE22 cells and isolated hypothalamic specimens were selected as in vitro models to conduct the experiments. The efficacy of citicoline, CAVAQ10, and vitamin B3, with their fixed combination, were assayed after the exposure of hypothalamic cells to hydrogen peroxide (concentration range 1 nM-10 µM), in order to evaluate the biocompatibility of treatments. The activity of neuroprotective and pro-inflammatory factors, namely, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα), involved in the neuronal cell damage in neurodegenerative diseases, were assayed in isolated hypothalamus. RESULTS: Neither citicoline, CAVAQ10, nor vitamin B3 significantly altered hypothalamic cell viability, thus suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study. In the same condition, citicoline and CAVAQ10 were also effective in reducing the gene expression of monoaminoxidase-B, involved in dopamine degradation. However, only citicoline demonstrated an ability to reduce dopamine levels. Conversely, all compounds were effective in reducing the gene expression of IL-6, and TNFα, and in inducing the gene expression of BDNF, with the co-administration of citicoline/CAVAQ10/vitamin B3 being generally more effective than single ingredients. CONCLUSIONS: The present findings support the beneficial and synergistic effects of citicoline, CAVAQ10, and vitamin B3 in fixed combination in reducing inflammation and oxidation, and in stimulating neurotrophin production in neuronal cells.

The acute dose and baseline amplitude-dependent effects of CDP-choline on deviance detection (MMN) in chronic schizophrenia: A pilot study.

The detection of deviant auditory features is empirically supported as impaired in schizophrenia and has been shown to associate with functional outcome. Modulated by glutamate neurotransmission, this sensory process has also been shown to relate to the α7 nicotinic acetylcholine receptor (nAChR) system, a prioritized molecular target for the development of novel cognition targeted pharmacological treatments. This pilot study assessed the acute effects of CDP-Choline, a choline supplement with α7 nAChR agonist properties, on the mismatch negativity (MMN), an event-related potential index of the detection of an acoustic change, in a sample of individuals diagnosed with chronic schizophrenia. Utilizing a randomized, placebo-controlled, double-blind design, the dose-dependent (500 mg, 1,000 mg, 2,000 mg), baseline amplitude-dependent (low vs. high), and deviant feature-dependent effects of CDP-Choline on the MMN were examined. CDP-choline's effects interacted with dosage, deviance feature, and baseline amplitude with low baseline amplitude patients demonstrating enhanced MMNs, and high baseline amplitude patients demonstrating suppressed MMNs in response to CDP-Choline. These findings offer tentative support for the involvement of the α7 nAChR system in auditory MMN abnormalities in schizophrenia and supports further research assessing the effects of long-term treatment with CDP-Choline in the personalized treatment of auditory deviance processing impairments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).