ascorbic-acid and Brain-Infarction

To compare clinical and morphological results of treatment of ischemic stroke in three groups of patients which differed by the forms and duration of an antioxidant therapy.. A randomized clinical trial was performed in 8 vascular centers of the Russian Federation in 2010-2014. It included 373 patients with ischemic stroke in the carotid territory. Patients were randomized into 3 groups to receive different regimens of antioxidant therapy as an adjunct to standard therapy: control group (ascorbic acid; 132 patients); cytoflavin (20 ml per day for 10 days; 133 patients); cytoflavin (the dose was decreased to 10 ml per day from 11th to 20th day) (108 patients). Patient's condition was assessed in 1, 10 and 21 day by a complex of clinical, laboratory and instrumental methods.. The analysis of CT in 1th and 21th day revealed a significant 1,5-1,7- fold decrease in the cerebral ischemic lesion in both groups treated with cytoflavin with no significant morphologic changes in the ascorbic acid group. The percentage of patients with ischemic lesion, increased during days 1-21, was 2-fold higher in the ascorbic acid group compared to cytoflavin groups. Morphologic changes were correlated with clinical variables and outcome. In patients with ≥14 points on NIH scale on admission, prolonged 20 day cytoflavin therapy was associated with a more prominent improvement of neurologic, functional and cognitive status compared to 10-day cytoflavin infusion. No differences in clinical variables were observed in patients with mild symptoms (<14 points on NIH scale on admission) receiving cytoflavin for 10 and 20 days.. Цель исследования - оценка антиоксидантной терапии (аскорбиновая кислота - АК, цитофлавин), назначаемой в составе стандартной схемы лечения по клиническим и морфологическим данным при инфаркте головного мозга. Материал и методы. Исследование проведено в период 2010-2014 гг. в 8 сосудистых центрах Российской Федерации. Были обследованы 373 пациента острым ишемическим инсультом в каротидном бассейне. Первую группу составили 132 пациента, получавшие 5% раствор АК в суточной дозе 20 мл, во вторую группу вошли 133 пациента, получавшие в качестве антиоксиданта цитофлавин в суточной дозе 20 мл в течение 10 дней, третью группу составили 108 пациентов, которым терапия цитофлавином была продолжена до 20 сут, при этом в период 11-20-е сутки заболевания доза препарата была уменьшена до 10 мл. Оценка состояния больных проводилась в динамике на основании комплекса клинических, лабораторных и инструментальных методов. Результаты и заключение. При анализе результатов рентгеновской компьютерной томографии, проводимой в 1-е и 21-е сутки лечения, было установлено, что назначение цитофлавина приводит к достоверному регрессу объема церебральной ишемии в среднем в 1,5-1,7 раза. В группе лечившихся АК значимых морфологических изменений не зарегистрировано, при этом среди лечившихся цитофлавином в 2 раза сократилась доля больных, у которых объем ишемии мозга возрастал в период 1-21 сут. У пациентов с первоначальной оценкой не менее 14 баллов по шкале NIH терапия цитофлавином в течение 20 дней способствовала более выраженной положительной динамике неврологического, функционального и когнитивного статуса, чем при 10-дневных инфузиях.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Brain Infarction; Drug Combinations; Energy Metabolism; Female; Flavin Mononucleotide; Humans; Infusions, Intravenous; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Russia; Succinates; Tomography, X-Ray Computed; Treatment Outcome

To determine the optimal duration of energy corrective treatment of ischemic stroke (II) with cytoflavin or ascorbic acid.. A multicenter randomized clinical trial included 185 patients, aged 40-75 years. Patients were randomized into 3 groups: the control group (n=64) received ascorbic acid; cytoflavin group 1 (n=72) was treated for 10 days and cytoflavin group 2 (n=49) for 20 days. In all groups, mean NIHSS score was 13, 42.2% of patients scored ≥14 and on admission, 42.2% of patients had consciousness impairment of different severity.. Cytoflavin treatment was more efficient than ascorbic acid that can be explained by different pharmacologic mechanisms. Treatment with cytoflavin for 10 days resulted in a significant decrease of ischemia zone volume by 25.2%, treatment with cytoflavin for 20 days - by 29.0%, which was associated with better outcomes in neurologic and functional status. Ascorbic acid demonstrated no effect on morphologic parameters. Prolonged treatment with cytoflavin in critically ill patients led to significant improvement in clinical and morphologic variables compared to the 10-day course. In patients with less severe condition comparable results were obtained.. Our data justify the need for personalized integrated antioxidant and energy correction therapy.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Brain Infarction; Brain Ischemia; Drug Combinations; Female; Flavin Mononucleotide; Humans; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Succinates; Treatment Outcome

Epidemiological studies have demonstrated that vitamin C decreases the risk of stroke, which has generally been ascribed to its function as antioxidant and free radical scavenger. However, whether there is a defined molecular target for vitamin C on stroke is unknown. Utilizing middle cerebral artery occlusion (MCAO) in rats as a model for ischemic stroke, we demonstrated that long-term, low-dose administration of vitamin C prior to MCAO could exert significant neuroprotective effect on the brain damage. The long-term, low-dose vitamin C pretreated rats had decreased brain infarct size and decreased neurological deficit score compared with the vehicle or single high dose pretreated MCAO rats. Furthermore, electrophysiological experiments using patch clamp technique showed that vitamin C increased the whole-cell current of the large-conductance Ca

Topics: Animals; Ascorbic Acid; Brain Infarction; CHO Cells; Cricetulus; Disease Models, Animal; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Male; Rats; Rats, Sprague-Dawley; Stroke

Cyclooxygenase-2 (COX-2) activity has been implicated in the pathogenesis of ischemic injury, but the exact mechanisms responsible for its toxicity remain unclear. Infection of primary neurons with an adenovirus expressing wild type (WT) COX-2 increased the susceptibility of neurons to hypoxia. Infection with an adenoviral vector expressing COX-2 with a mutation at the cyclooxygenase site did not increase susceptibility to hypoxia, whereas over-expression of COX-2 with a mutation in the peroxidase site produced similar susceptibility to hypoxia as WT COX-2. Primary neuronal cultures obtained from transgenic mice bearing a mutation in the COX-2 cylooxygenase site were protected from hypoxia. Mice with a mutation in the cyclooxygenase site had smaller infarctions 24 h after 70 min of middle cerebral artery occlusion than WT control mice. COX-2 activity had no effect on the formation of protein carbonyls. Ascorbate radicals were detected by electron paramagnetic resonance as a product of recombinant COX-2 activity and were blocked by COX-2 inhibitors. Similarly, formation of ascorbate radicals was inhibited in the presence of COX-2 inhibitors and in homogenates obtained from COX-2 null mice. Taken together, these results indicate that the cyclooxygenase activity of COX-2 is necessary to exacerbate neuronal hypoxia/ischemia injury rather than the peroxidase activity of the enzyme.

Topics: Animals; Arachidonic Acid; Ascorbic Acid; Brain Infarction; Catalytic Domain; Cell Line; Cells, Cultured; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Free Radicals; Humans; Hypoxia-Ischemia, Brain; Mice; Mice, Transgenic; Nerve Degeneration; Oxidative Stress; Peroxidase; Prostaglandin H2; Rats

EPC-K1, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl-hydrogen phosphate] potassium salt, is a novel antioxidant. In this study, we investigated a reduction of oxidative neuronal cell damage with EPC-K1 by immunohistochemical analysis for 8-hydroxy-2'-deoxyguanosine (8-OHdG) in rat brain with 60 min transient middle cerebral artery occlusion, in association with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) and staining for total and active caspase-3. Treatment with EPC-K1 (20 mg kg(-1) i.v.) significantly reduced infarct size (p < 0.05) at 24 h of reperfusion. There were no positive cells for 8-OHdG and TUNEL in sham-operated brain, but numerous cells became positive for 8-OHdG, TUNEL and caspase-3 in the brains with ischemia. The number was markedly reduced in the EPC-K1 treated group. These reductions were particularly evident in the border zone of the infarct area, but the degree of reduction was less in caspase-3 staining than in 8-OHdG and TUNEL stainings. These results indicate EPC-K1 attenuates oxidative neuronal cell damage and prevents neuronal cell death.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Apoptosis; Ascorbic Acid; Brain; Brain Infarction; Brain Ischemia; Caspase 3; Caspases; Deoxyguanosine; DNA Damage; Free Radicals; Immunohistochemistry; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Male; Nerve Degeneration; Neurons; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Vitamin E