flavin-mononucleotide and Brain-Ischemia

To evaluate the efficacy of including cytoflavin in rehabilitation measures in the early recovery period of patients with ischemic stroke.. Results of rehabilitation measures of 100 patients (50 women and 50 men, aged 18 to 85 years) in the early recovery period of ischemic stroke were analyzed. Psychological testing included NIHSS, MMSE, Rankin scale, Rivermead mobility index, exercise tolerance test. Depending on the rehabilitation scheme, patients were divided into the main group (n=50), who received a verticalization course and cytoflavin (intravenously, drip 20.0 ml in 250.0 ml 5% glucose for 14 days). The control group (n=50) included patients who received standard treatment.. Inclusion of cytoflavin in the rehabilitation scheme for patients with ischemic stroke increased the effectiveness of treatment, which was manifested by a decrease in the severity of neurological disorders assessed with NIHSS by 17.6% in the main group versus 10.8% in the control group (p<0.05) and recovery of cognitive functions assessed with MMSE by 5.8% versus 1.6%, respectively (p<0.05). In addition, there was a positive dynamics in the restoration of blood pressure (by 37.1% in the main group versus 30.6% in the control group (p<0.05)).. Цель исследования. Оценка эффективности включения препарата Цитофлавин в схемы реабилитационных мероприятий пациентов в раннем восстановительном периоде ишемического инсульта. Материал и методы. Проанализированы результаты реабилитационных мероприятий у 100 пациентов (50 женщин и 50 мужчин в возрасте от 18 до 85 лет) в раннем восстановительном периоде ишемического инсульта. Неврологическое и психологическое обследования включали следующие методики: шкалы NIHSS, MMSE и Рэнкина, индекс мобильности Ривермид и тест на толерантность к физическим нагрузкам. В зависимости от схемы реабилитации пациенты были разделены на две группы. В основную группу вошли 50 пациентов, получивших курс вертикализации и Цитофлавин: внутривенно, капельно 20,0 мл в 250,0 мл 5% глюкозы в течение 14 сут. Группу сравнения составили 50 больных, получивших стандартный курс реабилитации. Результаты и заключение. Включение Цитофлавина в схему реабилитации пациентов с ишемическим инсультом повысило эффективность лечения, что проявилось уменьшением выраженности неврологических нарушений (по шкале NIHSS) на 17,6% в основной группе против 10,8% в группе сравнения (р<0,05) и восстановлением когнитивных функций (по шкале ММSE) на 5,8% против 1,6% соответственно (р<0,05). Кроме того, была отмечена положительная динамика восстановления артериального давления - на 37,1% в основной группе против 30,6% в группе сравнения (р<0,05).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Pressure; Brain Ischemia; Cognition; Drug Combinations; Female; Flavin Mononucleotide; Humans; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Stroke; Stroke Rehabilitation; Succinates; Treatment Outcome; Young Adult

To evaluate the efficacy of cytoflavin in the treatment of hypoxic-ischemic lesions of the nervous system in young infants with transient neonatal hypothyroidism.. Authors analyzed the efficacy of cytoflavin in the treatment of cerebral ischemia in the combination with transient neonatal hypothyroidism in 89 newborns. The main group comprised 43 children treated with intravenous cytoflavin in dose 2 ml per 1 kg of body weight per day for five days; 46 newborns of the comparison group received basic therapy.. It was found that the moderate depression of motor activity and autonomic-visceral dysfunctions were the leading clinical neurological manifestations in these groups. In the main group, there was a significantly more rapid decline of hyperthyreotropinemia, indirect hyperbilirubinemia, reduced severity of cerebral ischemia by the results of neurosonography on the 5th or 6th day and regression of the main clinical symptoms compared to the control group. The positive neuroprotective and thyroid protective effect of cytoflavin, good tolerability and its compatibility with other drugs used in the standard treatment of hypoxic-ischemic lesions of the central nervous system were identified.. Цель исследования - оценка эффективности цитофлавина в терапии гипоксически-ишемических поражений нервной системы у детей 1-го месяца жизни с транзиторным неонатальным гипотиреозом. Материал и методы. Проведен анализ эффективности терапии цитофлавином церебральной ишемии в сочетании с транзиторным неонатальным гипотиреозом у 89 новорожденных 1-го месяца жизни. Основную группу составили 43 ребенка, получавших внутривенно цитофлавин из расчета 2 мл на 1 кг массы тела в сутки в течение 5 дней; 46 новорожденным группы контроля проводилась базисная терапия. Результаты и заключение. Выявлено, что ведущими клиническими неврологическими проявлениями в исследуемых группах были умеренно выраженный синдром угнетения двигательной активности и вегетовисцеральные дисфункции. В основной группе отмечено достоверно более быстрое снижение гипертиреотропинемии, непрямой гипербилирубинемии, уменьшение степени выраженности церебральной ишемии при нейросонографическом исследовании на 5-6-е сутки и больший регресс основных клинических симптомов по сравнению с контрольной группой. Отмечены положительное нейропротективное и тиреопротективное действие цитофлавина, хорошая переносимость препарата и его совместимость с другими лекарственными средствами, используемыми в стандартном лечении гипоксически-ишемических поражений ЦНС.

Topics: Antioxidants; Brain Ischemia; Congenital Hypothyroidism; Drug Combinations; Female; Flavin Mononucleotide; Humans; Infant; Infant, Newborn; Inosine Diphosphate; Male; Motor Activity; Niacinamide; Succinates; Treatment Outcome

To study an effect of nonspecific cytoprotective therapy on clinical manifestations, disease course and indicators of stress system in patients with different stages of chronic cerebral ischemia (CCI).. Authors examined 266 patients with CCI, aged from 35 to 55 years. The patients received basic and nonspecific cytoprotective therapy. The dynamics of subjective and objective symptoms of encephalopathy, clinical outcomes after a year of observation, and the state of stress system were analyzed. An effect of therapy on stress was assessed by the dynamics of blood pressure reactions to stress.. An open randomized comparative study has shown that the inclusion of the drug with nonspecific cytoprotective actions (cytoflavin) in the therapeutic complex improves the therapeutic effect on the clinical manifestations of CCI. The higher frequency of favorable outcomes over one year of follow-up is associated with the optimization of stress system activity under nonspecific cytoprotective therapy and the increase in stress resistance.. Цель исследования - изучить влияние неспецифической цитопротективной терапии на клинические проявления, характер течения заболевания и показатели стрессовой системы у пациентов с разными стадиями хронической ишемии головного мозга (ХИМ). Материал и методы. Обследованы 266 пациентов с ХИМ в возрасте от 35 до 55 лет, получавших базисную и неспецифическую цитопротективную терапию. Была проанализирована динамика субъективных и объективных симптомов ХИМ, клинические исходы через 1 год наблюдения и состояние стрессовой системы. Влияние терапии на стрессоустойчивость оценивали по динамике стрессовых реакций крови. Результаты и заключение. В результате открытого, сравнительного рандомизированного исследования показано, что включение в терапевтический комплекс препарата неспецифического цитопротективного действия (цитофлавин) повышает эффективность воздействия на клинические проявления ХИМ. Повышение числа благоприятных исходов через 1 год наблюдения было ассоциировано с оптимизацией деятельности стрессовой системы при применении неспецифической цитопротективной терапии и повышением стрессоустойчивости.

Topics: Adult; Antioxidants; Brain Ischemia; Chronic Disease; Drug Combinations; Female; Flavin Mononucleotide; Humans; Inosine Diphosphate; Male; Middle Aged; Neuroprotective Agents; Niacinamide; Stress, Physiological; Succinates; 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

Authors compared cognitive functions in 60 patients (main group) with different stages of discirculatory encephalopathy (DE), I, II and III stages. A comparison group included 10 age-matched normals without DE. All patients underwent a clinical-neurological investigation and performed neuropsychological tests (MMSE, the Clock drawing test, Burdon probe) and Spilberger-Khanin test. Cognitive evoked potentials, including P300, were recorded. Results revealed the decrease in performance on neuropsychological tests and P300 components that indicated the slowing of metabolic processes in the cerebral cells of patients with DE. In patients treated with cytoflavin, the activation of metabolic processes in the brain cells that indicated the protection of the cellular cluster clinically manifested itself in neurocognitive and electrophysiological improvements was observed.

Topics: Acoustic Stimulation; Brain Ischemia; Cognition; Cognitive Dysfunction; Drug Combinations; Evoked Potentials; Female; Flavin Mononucleotide; Follow-Up Studies; Humans; Inosine Diphosphate; Male; Middle Aged; Neuropsychological Tests; Niacinamide; Succinates; Treatment Outcome

Sixty patients with chronic brain ischemia (discirculatory encephalopathy, I and II stages) were enrolled in the study. Patients of the first group (n=30) were treated with cytoflavin and patients of the second group (n=30) received piracetam prescribed first as injections and then in pills. The treatment duration was 35 days. Standard neurological examination and psychometric assessment of patients and dopplerography of cerebral vessels were carried out. Cytoflavin was shown to have a positive effect on the neurological status. It decreases asthenic, cephalgia and vestibulo-cerebellar syndromes as well as neurological and emotional disturbances reducing the symptoms of depression and anxiety and improving cognitive functions and memory as well as quality of life of patients. The changes were significant compared to those in the group of patients treated with piracetam.

Topics: Brain; Brain Ischemia; Chronic Disease; Drug Combinations; Female; Flavin Mononucleotide; Hemodynamics; Humans; Inosine Diphosphate; Male; Middle Aged; Niacinamide; Psychiatric Status Rating Scales; Regional Blood Flow; Succinates; Treatment Outcome

Considerable disturbance of all quality of life domains that worsens social adaptation and daily living and results in an asthenic-neurotic syndrome, along with neurologic and mnestic-intellectual disturbances, was revealed in patients with chronic brain ischemia (stages I, II, III). Based on the results of the double blind placebo-controlled trial, the high clinical efficacy of cytoflavin in patients with chronic brain ischemia has been shown. The treatment with cytoflavin decreases the severity of subjective symptoms and complaints thus increasing the working ability of patients, improves balance and gait, decreases the severity of asthenic and neurotic syndromes, improves cognitive and memory functions (information storage, reasoning and attention), positively effects on quality of sleep and all aspects of quality of life, in particular, on physical activity, self-rating of health and viability as well as social activity, mental health and emotional lability.

Topics: Antioxidants; Brain Ischemia; Cognition; Drug Combinations; Female; Flavin Mononucleotide; Humans; Inosine Diphosphate; Male; Niacinamide; Succinates; Treatment Outcome

Topics: Antioxidants; Brain Ischemia; Chronic Disease; Drug Combinations; Flavin Mononucleotide; Humans; Inosine Diphosphate; Neuroprotective Agents; Niacinamide; Succinates

To assess an effect of cytoflavin on the results of rehabilitation treatment and the increase in exercise tolerance in patients with stroke complicated by post-intensive care syndrome (PICS).. The data of 53 patients who underwent neurorehabilitation in the ICU after ischemic stroke were analyzed. Depending on the treatment regimen, the patients were divided into two groups. Group 1 (main,. The components of the energytropic effect of cytoflavin can have a positive modulating effect, increasing the tolerance of rehabilitation measures for the treatment of PICS in patients with ischemic stroke. Further research is required.. Оценка влияния Цитофлавина на результаты реабилитационного лечения и повышение толерантности к физической нагрузке у пациентов с инсультом, осложненным синдромом после интенсивной терапии (ПИТ).. Проанализированы данные 53 пациентов, прошедших нейрореабилитацию в условиях отделения реанимации и интенсивной терапии после ишемического инсульта. В зависимости от схемы лечения больные были разделены на 2 группы: основную (

Topics: Brain Ischemia; Critical Care; Drug Combinations; Flavin Mononucleotide; Humans; Inosine Diphosphate; Niacinamide; Stroke; Stroke Rehabilitation; Succinates; Treatment Outcome

To study the effectiveness of intraoperative administration of Cytoflavine for the prevention of ischemic brain injury during cerebral aneurysm (CA) clipping with temporary occlusion of the leading artery under general anesthesia.. The prospective cohort single-center study included 40 patients with CA ( the main group - 27 patients with intraoperative administration of cytoflavine; the comparison group -13 patients without use of cytoflavine), who underwent aneurism clipping with temporary occlusion of the afferent artery. We assesed the intraoperative state of the brain, the time of awakening and extubation of patients after surgery, neurological deficit and local ischemic changes in the area of surgery according to the CT of the brain in the early postoperative period, resuscitation bed-day and the relationship of these indicators with the duration of temporary occlusion of the afferent artery in the selected groups of patients.. In intergroup comparison, patients of the main group treated with intraoperative cytoflavin showed a reduction in the time of awakening (p=0.013) and the time of extubation (p=0.01) both with temporary occlusion of the afferent artery and in patients without temporary occlusion (p<0.05). The duration of resuscitation bed-day decreased in the main group of patients receiving intraoperatively cytoflavine (p=0.01), as well as in patients in the comparison group without temporary occlusion (p<0.05).. Temporary occlusion of the afferent artery with short intervals of vessel occlusion in combination with intraoperative intravenous administration of cytoflavine expands the tolerability to artery occlusion in patients operated in the 'cold' period, reduces the possibility of neurological deficit, reduces the recovery period and resuscitation bed-day after surgical clipping CA.. Цель исследования - изучение эффективности интраоперационного введения препарата цитофлавин для профилактики ишемического повреждения головного мозга при нейрохирургических операциях клипирования церебральной аневризмы (ЦА) с использованием временной окклюзии приводящей артерии в условиях общей анестезии. Материал и методы. В проспективное когортное одноцентровое исследование включены 40 пациентов с ЦА (основная группа - 27 больных с интраоперационным введением цитофлавина; группа сравнения - 13 пациентов без использования цитофлавина), оперированных открытым способом с плановым использованием методики временной окклюзии питающей аневризму артерии. Определяли интраоперационное состояние мозга, сроки пробуждения и экстубации больных после выполнения хирургического вмешательства, неврологический дефицит и локальные ишемические изменения в зоне оперативного вмешательства по данным СКТ головного мозга в раннем послеоперационном периоде, реанимационный койко-день и взаимосвязь этих показателей с длительностью временной окклюзии приводящей артерии в выделенных группах пациентов. Результаты. При межгрупповом сравнении у пациентов основной группы, получавших интраоперационно цитофлавин, отмечено сокращение сроков пробуждения (p=0,013) и экстубации (p=0,01) как с временной окклюзией питающей аневризму артерии, так и без временного клипирования приводящего сосуда (p<0,05). Продолжительность реанимационного койко-дня уменьшалась в основной группе пациентов, получавших интраоперационно препарат цитофлавин (p=0,01), а также у больных в группе сравнения без временного клипирования (p<0,05). Выводы. Временное клипирование питающей аневризму артерии с короткими интервалами окклюзии сосуда в сочетании с интраоперационным внутривенным введением цитофлавина расширяет переносимость окклюзии артерии у пациентов, оперированных в 'холодном' периоде, уменьшает возможности возникновения неврологического дефицита, сокращает сроки восстановительного периода и реанимационного койко-дня после оперативного лечения клипирования ЦА.

Topics: Brain; Brain Injuries; Brain Ischemia; Drug Combinations; Flavin Mononucleotide; Humans; Inosine Diphosphate; Intracranial Aneurysm; Intraoperative Care; Neuroprotective Agents; Neurosurgical Procedures; Niacinamide; Prospective Studies; Succinates; Suture Techniques

Ischemic brain injury is characterized by 2 temporally distinct but interrelated phases: ischemia (primary energy failure) and reperfusion (secondary energy failure). Loss of cerebral blood flow leads to decreased oxygen levels and energy crisis in the ischemic area, initiating a sequence of pathophysiological events that after reoxygenation lead to ischemia/reperfusion (I/R) brain damage. Mitochondrial impairment and oxidative stress are known to be early events in I/R injury. However, the biochemical mechanisms of mitochondria damage in I/R are not completely understood.. We used a mouse model of transient focal cerebral ischemia to investigate acute I/R-induced changes of mitochondrial function, focusing on mechanisms of primary and secondary energy failure.. Ischemia induced a reversible loss of flavin mononucleotide from mitochondrial complex I leading to a transient decrease in its enzymatic activity, which is rapidly reversed on reoxygenation. Reestablishing blood flow led to a reversible oxidative modification of mitochondrial complex I thiol residues and inhibition of the enzyme. Administration of glutathione-ethyl ester at the onset of reperfusion prevented the decline of complex I activity and was associated with smaller infarct size and improved neurological outcome, suggesting that decreased oxidation of complex I thiols during I/R-induced oxidative stress may contribute to the neuroprotective effect of glutathione ester.. Our results unveil a key role of mitochondrial complex I in the development of I/R brain injury and provide the mechanistic basis for the well-established mitochondrial dysfunction caused by I/R. Targeting the functional integrity of complex I in the early phase of reperfusion may provide a novel therapeutic strategy to prevent tissue injury after stroke.

Topics: Animals; Brain; Brain Ischemia; Cerebrovascular Circulation; Citrate (si)-Synthase; Disease Models, Animal; Electron Transport Complex I; Energy Metabolism; Flavin Mononucleotide; Glutathione; Infarction, Middle Cerebral Artery; Male; Mice; Mitochondria; Oxidative Stress; Random Allocation; Reperfusion Injury; Sulfhydryl Compounds

Analysis of stress-releasing blood reactions (electrophoretic mobility of red blood cells, WBC count, and leukocyte ratio) in rats with experimental cerebral ischernia under the action of cytoflavin held showed that cytoflavin in combination with basic therapy leads to further activation of compensatory-adaptive reactions of the body and stimulated peripheral stress-limiting mechanisms.

Topics: Animals; Brain Ischemia; Chronic Disease; Drug Combinations; Erythrocytes; Flavin Mononucleotide; Inosine Diphosphate; Leukocyte Count; Male; Niacinamide; Rats; Rats, Wistar; Succinates

The article deals with the results of analysis of electrophoretic mobility of erythrocytes and leukogram in patients with dyscirculatory encephalopathy on different stages of disease on application therapy with inclusion of stress-modulating pharmaceuticals into course of treatment. It is established that the electrophoretic mobiliy of erythrocytes makes it possible to evaluate the adaptive indicators blood in patients with dyscirculatory encephalopathy. The consideration of these indicators makes feasible the substantiation of inclusion of stress-modulating therapy into complex treatment of patients with chronic cerebrovascular inefficiency.

Topics: Adult; Brain Ischemia; Chronic Disease; Delta Sleep-Inducing Peptide; Drug Combinations; Erythrocytes; Flavin Mononucleotide; Glycine; Humans; Inosine Diphosphate; Middle Aged; Niacinamide; Succinates

This study investigated efficiency of cytoflavin in combined treatment of acute hemisphere or stem stroke. It included 35 patients aged 40-70 years with the newly diagnosed mild and moderate stroke. The main group comprised 29 patients treated with cytoflavin (10 ml twice daily by i/v drop infusion for 10 days) in addition to basal therapy. Controls (n=15) were given basal therapy alone. All patients were examined on days 1 and 15 for the evaluation of their neurological status, neuropsychological testing, assessment of cognitive function (from the ability to remember 10 words), everyday activities, and quality of life (based on the QOL scale). Evaluation of the neurological status by the NIHSS scale on day 15 after the onset of therapy revealed its positive dynamics. Indicators of functional normalization in groups 1 and 2 were significantly different. Analysis of social and functional activities on day 15 demonstrated a higher Bartel index in patients given cytoflavin. Moreover these patients showed significant improvement of short- and long-term memory as well as the highest health index. The MMSE test did not reveal significant difference between the two groups on day 15 (p > 0.05). It is concluded that cytoflavin therapy significantly improved the health status of the patients. It proved efficacious as regards correction of motor and non-motor symptoms in patients having acute ischemic stroke.

Topics: Acute Disease; Adult; Aged; Brain Ischemia; Drug Combinations; Electroencephalography; Flavin Mononucleotide; Follow-Up Studies; Humans; Inosine Diphosphate; Middle Aged; Niacinamide; Succinates; Tomography, X-Ray Computed; Treatment Outcome

A study of free radical processes (FRP) markers in 381 patients with ischemic and hemorrhagic stroke revealed the importance of oxidant stress that was most severe in patients with large volumes of stroke. Intensification of FRP consists in the reduction or inversion of oxygen FRP activity and increase in lipid free radical FRP that last till the patient discharge from a hospital. FRP indicators are early prognostic markers of stroke course and outcome. An inverse correlation between the level of anti peroxide plasma activity (APA) and the dynamics of the increase in stroke lesion from 1 to 20 days, and direct correlation between malondialdehyde (MDA) titer and the risk of hemorrhagic transformation and growth of the lesion from 5 to 20 days of disease were revealed. The results indicate that inclusion of antoixidant therapy should be conducted as early as possible after stroke using high doses of drugs in severe cases. The high efficacy of antioxidant cytoflavin in a daily dose of 20 ml in patients with stroke of different character and severity was shown. The positive effect of cytoflavin on FRP markers was accompanied by the improvement of clinical and morphological presentations and stroke outcome.

Topics: Aged; Antioxidants; Biomarkers; Brain Ischemia; Drug Combinations; Female; Flavin Mononucleotide; Free Radicals; Humans; Inosine Diphosphate; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Malondialdehyde; Middle Aged; Niacinamide; Prognosis; Stroke; Succinates

The author presents results of multicentre randomized studies of therapeutic efficiency of cytoflavin tablets in patients with chronic cerebral ischemia including asthenovegetative syndrome. Cytoflavin was shown to reduce clinical manifestations of asthenia, anxiety, depression, cognitive and emotional disorders and simultaneously improve quality of life. The efficiency of cytoflavin is confirmed by improved physical and psychic state of the patients, their enhanced social activity.

Topics: Asthenia; Brain Ischemia; Chronic Disease; Drug Combinations; Flavin Mononucleotide; Humans; Inosine Diphosphate; Multicenter Studies as Topic; Neuropsychological Tests; Niacinamide; Quality of Life; Randomized Controlled Trials as Topic; Succinates

A multicenter trial involving 30 newborns with post-hypoxic myocardial lesions associated with I-II degree cerebral ischemia has revealed that the inclusion of cytoflavin infusions into the complex standard treatment leads, besides the improvement of general clinical status, to significantly more rapid, as compared to the control group, positive dynamics of pump and contractile myocardial functions, elimination of hyperenzymemia, hypoxia and electrical instability of the myocardium, decrease in energetic deficit, and repolarization changes within the first 5 days of in-hospital therapy as well as during the follow-up from 1 to 6 months of life.

Topics: Brain Ischemia; Drug Combinations; Female; Flavin Mononucleotide; Follow-Up Studies; Heart; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inosine Diphosphate; Male; Myocardial Contraction; Myocardium; Niacinamide; Succinates

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

Cytoflavin and neuronol produce vasoactive and neuroprotective effects in rats with cerebral ischemia. Vasoactive activity of neuronol was higher than that of cytoflavin. These differences were most pronounced at the level of microcirculation. Test preparations were equally potent in producing the neuroprotective effect. Cytoflavin and neuronol markedly decreased the mortality rate of animals. Over the first 6 h of ischemia the relative effectiveness of cytoflavin was higher than that of neuronol. However, neuronol exceeded cytoflavin in the relative effectiveness during the follow-up period (days 1-21).

Topics: Animals; Brain; Brain Ischemia; Cerebrovascular Circulation; Drug Combinations; Flavin Mononucleotide; Inosine Diphosphate; Male; Neuroprotective Agents; Niacinamide; Rats; Regional Blood Flow; Reperfusion Injury; Succinates; Succinic Acid; Survival Rate

The present studies examined the hypothesis that the distribution of cerebral injury after a focal ischemic insult is associated with the regional distribution of nitric oxide synthase (NOS) activity.. Based on previous studies that certain anatomically well-defined areas are prone to become either core or penumbra after middle cerebral artery occlusion (MCAO), we measured NOS activity in these areas from the right and left hemispheres in a spontaneously hypertensive rat filament model. Four groups were studied: (1) controls (immediate decapitation); (2) 1.5 hours of MCAO with no reperfusion (R0); (3) 1.5 hours of MCAO with 0.5 hour of reperfusion (R0.5); and (4) 1.5 hours of MCAO with 24 hours of reperfusion (R24). Three groups of corresponding isoflurane sham controls were also included: 1.5 (S1.5) or 2 (S2.0) hours of anesthesia and 1.5 hours of anesthesia+24 hours of observation (S24).. Control core NOS activity for combined right and left hemispheres was 129% greater than penumbral NOS activity (P<0.05). Combined core NOS activity was also greater (P<0.05) in the three sham groups: 208%, 122%, and 161%, respectively. In the three MCAO groups, ischemic and nonischemic core NOS remained higher than penumbral regions (P<0.05). However, NOS activity was lower in the ischemic than in the nonischemic core in all three groups: R0 (29% lower), R0.5 (48%), and R24 (86%) (P<0.05). Addition of cofactors (10 micromol/L tetrahydrobiopterin, 3 micromol/L flavin adenine dinucleotide, and 3 micromol/L flavin mononucleotide) increased NOS activity in all groups and lessened the decrease in ischemic core and penumbral NOS.. Greater NOS activity in core regions could explain in part the increased vulnerability of that region to ischemia and could theoretically contribute to the progression of the infarct over time. The data also suggest that NOS activity during ischemia and reperfusion could be influenced by the availability of cofactors.

Topics: Anesthetics, Inhalation; Animals; Antioxidants; Arterial Occlusive Diseases; Biopterins; Brain Ischemia; Cerebral Arteries; Cricetinae; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Isoflurane; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Rats; Rats, Inbred SHR; Reperfusion; Reperfusion Injury; Time Factors