Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke

Abstract

Ischemic stroke is considered as one of the most frequent and severe complications of atrial fibrillation. The present study was undertaken to examine whether post-insult treatment with cytidine diphosphate-choline (CDP-choline, or citicoline) affects serum levels of the angiogenesis inhibitor angiostatin and neurospecific proteins as markers of brain damage in patients with cerebral ischemia associated with atrial fibrillation. Thirty-three patients with a diagnosis of acute ischemic stroke received citicoline sodium by intravenous infusions (1,000 mg daily for 14 days) in addition to the standard treatment (basic group). Twentyfive patients with the same pathologies, who received only standard therapy, were enrolled in the study as a control group. Serum content of angiostatin and neurospecific proteins, namely neurofilament heavy subunit (NF-H) and glial fibrillary acidic protein (GFAP), was measured by immunoblotting at the basal level and after the treatment. Citicoline treatment caused significant decreases in serum levels of angiostatin (by 40% vs. basal level, P < 0.05), GFAP (by 61%, P < 0.01), and the NF-H subunit (by 19%, P < 0.05) and had no effect on the serum albumin content. In contrast, there were no statistically significant differences between baseline levels of the studied protein markers and their content after the treatment period in the control group. These findings indicate for the first time that CDP-choline protects both astrocytes and neurons and improves angiogenic capacity through down-regulation of angiostatin in post-ischemic patients with atrial fibrillation after acute ischemic stroke. Further studies are needed to test associations between serum levels of these biomarkers, clinical outcomes, and treatment efficacy of stroke. K e y w o r d s: atrial fibrillation, ischemic stroke, citicoline, angiostatin, neurofilaments (NFs), glial fibrillary acidic protein (GFAP).I schemic stroke is a complex multifactorial and polygenic disease. It is generally accepted that one of the major risk factors for ischemic stroke is atrial fibrillation [1]. Past studies indicate that fibrillation of the atrium produces stasis of blood, which causes thrombus formation and embolism in the brain [2,3]. More recent investigations suggest that the pathogenesis of stroke in atrial fibrillation is more complicated and involves other factors in addition to the dysrhythmia [4,5]. It is well acknowled ged that atrial fibrillation is the most prevalent car-diac arrhythmia, affecting approximately 12% of the population worldwide. Being an independent risk factor for stroke, atrial fibrillation is associated with high mortality, morbidity, and socioeconomic burden [6]. Therefore, stroke prevention with appropriate prophylaxis remains central to management of both atrial fibrillation and its neurological complications. However, the search for effective neuroprotectors remains frustrating, and the current therapeutic protocols remain suboptimal. Ideally, sufficient protection must be provided to the ischemic brain a...

Application of Citicoline in Neurological Disorders: A Systematic Review

“…On this basis, the authors concluded that citicoline has a protective effect on astrocytes and neurons. Moreover, it has a beneficial impact on the regulation of angiogenesis in an ischemically damaged brain [ 36 ].…”

Serum Levels of the Biomarkers Associated with Astrocytosis, Neurodegeneration, and Demyelination: Neurological Benefits of Citicoline Treatment of Patients with Ischemic Stroke and Atrial Fibrillation

“…An important effect of citicoline in ischemic stroke provides certain improvement of cerebral perfusion [11]. In our recent study, citicoline was shown to decrease the circulating levels of angiostatin in patients with ischemic stroke [38]. Angiostatin is a proteolytically-derived fragment of the large protein plasminogen, which acts as a potent inhibitor of migration and proliferation of endothelial cells, and may suppress the collateral formation in ischemic tissues [39].…”

Citicolina: revisión farmacológica y clínica, actualización 2022

“…Arcadi et al [ 599 ] in a retrospective cohort study concluded that the administration of nootropic drugs, such as citicoline, could be a valid therapeutic strategy to manage post-stroke patients suffering from mild-moderate anxiety or anxious-depressive syndrome. Tykhomyrov et al [ 600 ] indicated for the first time that citicoline protects both astrocytes and neurons and improves angiogenic capacity through down-regulation of angiostatin in post-ischemic patients with atrial fibrillation after acute ischemic stroke.…”

“…Arcadi et al [ 599 ], en un estudio de cohorte retrospectivo, concluyeron que la administración de fármacos noótropos, como la citicolina, podría ser una estrategia terapéutica válida para el manejo de pacientes postictus con ansiedad leve-moderada o síndrome ansiosodepresivo. Tykhomyrov et al [ 600 ] indicaron por primera vez que la citicolina protege tanto a los astrocitos como a las neuronas y mejora la capacidad angiógena a través de la regulación a la baja de la angiostatina en pacientes postisquémicos con fibrilación auricular después de un accidente cerebrovascular isquémico agudo.…”