Potential Efficacy of Citicoline as Adjunct Therapy in Treatment of Cerebral Malaria

El‐Assaad, Fatima; Combes, Valéry; Grau, Georges E.; Jambou, Ronan

doi:10.1128/aac.02591-12

Cited by 9 publications

(12 citation statements)

References 33 publications

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“…In this study, Citicoline treatment led to diminished Annexin V/ PI fluorescence intensity, indicating the ability of Citicoline to lower apoptotic cell death in transmitochondrial AMD cells. This is consistent with a previous study in which the apoptosis inhibitory action of Citicoline was demonstrated using Annexin V/ FITC Flow cytometry analysis in a mouse model of cerebral malaria (CM); administration of Citicoline rescued cells in an experimental model of CM in vitro as well conferred partial protection against cell death and neurological syndrome in murine CM [17].…”

Section: Discussionsupporting

confidence: 92%

Role of Citicoline in an in vitro AMD model

Nashine

Kenney

2020

Aging

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Citicoline is the exogenous form of the nootropic, Cytidine 5'-diphosphate-choline that exerts its neuroprotective effects in the brain as well as in the eye. The current study characterized the cytoprotective effects of purified Citicoline in transmitochondrial AMD (Age-related Macular Degeneration) RPE cybrid cells which carry diseased mitochondria from clinically characterized AMD patients. The effects of Citicoline were examined via flow cytometry analysis of AnnexinV/ PI-stained cells, IncuCyte live-cell imaging analysis to quantify cells undergoing caspase-3/7-mediated apoptosis, analyses of gene expression profiles of apoptosis, hypoxia, and angiogenesis markers, and measurement of ROS levels and cell viability. Our results demonstrated that Citicoline when added exogenously alleviates apoptotic effects as evidenced by diminished AnnexinV/PI and Caspase-3/7 staining, downregulation of apoptosis genes, enhanced cell viability, and reduced oxidative stress in AMD RPE cybrid cells. In conclusion, our study identified Citicoline as a protector in AMD RPE cybrid cells in vitro. However, further studies are required to establish the merit of Citicoline as a cytoprotective molecule in AMD and to decipher the molecular underpinnings of its mechanism of action in AMD.

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Section: Discussionsupporting

confidence: 92%

Role of Citicoline in an in vitro AMD model

Nashine

Kenney

2020

Aging

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“…In vivo experiments showed that mice treated with pantethine 24 h post-infection with P. berghei did not display any signs of CM, which was attributed to two crucial events: diminished platelet reactivity, and downregulated EV production [ 83 ]. Another compound, citicoline, was found to reduce EV production in human brain ECs in vitro, and significantly enhance survival of mice with CM when used in combination with artesunate [ 85 ]. Citicoline is a widely available dietary supplement that occurs naturally in eukaryotic cell membranes and plays a role in membrane stability.…”

Section: The Pathogenesis Of Malaria: a Potential Role For Evsmentioning

confidence: 99%

Extracellular vesicles in malaria: an agglomeration of two decades of research

Opadokun

Rohrbach

2021

Malar J

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Malaria is a complex parasitic disease, caused by Plasmodium spp. More than a century after the discovery of malaria parasites, this disease continues to pose a global public health problem and the pathogenesis of the severe forms of malaria remains incompletely understood. Extracellular vesicles (EVs), including exosomes and microvesicles, have been increasingly researched in the field of malaria in a bid to fill these knowledge gaps. EVs released from Plasmodium-infected red blood cells and other host cells during malaria infection are now believed to play key roles in disease pathogenesis and are suggested as vital components of the biology of Plasmodium spp. Malaria-derived EVs have been identified as potential disease biomarkers and therapeutic tools. In this review, key findings of malaria EV studies over the last 20 years are summarized and critically analysed. Outstanding areas of research into EV biology are identified. Unexplored EV research foci for the future that will contribute to consolidating the potential for EVs as agents in malaria prevention and control are proposed.

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“…Adjunct treatments that act through alternate mechanisms and address one or more of the pathogenic processes are urgently needed for a full rate recovery. Till date, a number of agents such as exogenous nitric oxide (NO) donor-dipropylenetriamine-NONOate (Zanini et al 2012), membrane stabilizer citicoline (El-Assaad et al 2014), mTOR inhibitor rapamycin (Gordon et al 2015) have been tested in ECM model as effective adjunct treatment. Atorvastatin, a lipid-lowering agent prevents cytoadhesion and endothelial damage under in vitro condition (Taoufiq et al 2011) and had shown protection in ECM model in combination with dihydroartemisinin (Dormoi et al 2013) and mefloquine (Souraud et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Potential cerebral malaria therapy: intramuscular arteether and vitamin D co-administration

et al. 2016

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Cerebral malaria (CM) shows lethality rate of 15-25% despite effective antimalarial chemotherapy. The effective adjunct treatment to counteract the CM pathogenesis is urgently required. In murine CM model, most interventions studied till date are administered before the onset of CM symptoms, which belittle its translational value to human. We studied intramuscular arteether-vitamin D (ART-VD) combination treatment for CM outcome improvement after the onset of neurological symptoms. The intramuscular dose of 50 µg kg-1 VD for 3 days combined with a loading dose of 25 mg kg-1 α/β arteether followed by 12·5 mg kg-1 dose for two consecutive days led to significant improvement in survival (73% in combination group vs 29 and 0% in arteether and VD monotherapy, respectively) and clinical recovery. The treatment in all the groups partially restored the blood-brain barrier integrity and reduced the level of serum proinflammatory cytokines tumour necrosis factor-α and interferon-γ. The brain transcripts of inflammatory chemokines viz. CXCL10, CXCL9, CCL4 and CCL5 and T cell migration in the brain microvasculature were significantly diminished in all the treatment groups. ART-VD treatment significantly reduced intercellular cell adhesion molecule-1 expression. Taken together, our findings show that coordinated actions of ART-VD improve the outcome of experimental CM.

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Potential Efficacy of Citicoline as Adjunct Therapy in Treatment of Cerebral Malaria

Cited by 9 publications

References 33 publications

Role of Citicoline in an in vitro AMD model

Role of Citicoline in an in vitro AMD model

Extracellular vesicles in malaria: an agglomeration of two decades of research

Potential cerebral malaria therapy: intramuscular arteether and vitamin D co-administration

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