Тhе possibility of treatment of cognitive impairment in the complex therapy of patients with the consequences of cerebral infarction
Author:
Е.В. KUZNETSOVA, Е.А. SALINA, I.I. SHOLOMOV.
Saratov State Medical University of the Russian Health Protection, Neurology Chair.
Summary:
Objective. То study neuropsychological status of inpatients with the consequences of сеrеbrаl infarction treated with cortexin аnd mexidol. Material аnd methods. We carried out а neurological аnd neuropsychological examination of 62 patients with the consequences of cerebral infarction treated with cortexin in the dose of 10 mg and mexidol in the dose of 5 ml of 5% solution intravenously during 15 days. Results аnd conclusion. It has bееn shown that the use of this drug combination decreases complaints аnd neurological symptoms аnd significantly improves cognitive аnd emotional status as well. The more positive changes аrе related to attention, speed of mental reactions, anxiety аnd verbal activity. The complextherapy with cortexin аnd mexidol decreased neurological deficit аnd improve cognitive functioning and psychoemotional status thus increasing quality of life аnd rehabilitation potential of the patients.
Keywords: consequences of сеrеbral infarction, cognitive impairment, emotional status, cortexin, mexidol.
Modern strategies of protection of hypoxic-ischemic brain damage
Author:
S.N. YANISHEVSKY, N.V. TSYGAN, S.YU. GOLOKHVASTOV, R.V. ANDREEV, I.V. LITVINENKO, O.S. KARPOVA, V.A. YAKOVLEVA.
Kirov Military Medical Academy, St. Petersburg, Russia.
Summary:
Nowadays, there are two complementary approaches to treatment of patients with ischemic stroke: reperfusion and neuroprotection. The main purpose of neuroprotection is to intervene ischemic cascade at every stage of the pathological process and thus avoid the death of nerve cells and expand the therapeutic window for reperfusion therapy. The use of drugs with neurotrophic, antioxidant and neuroregenerative effects is pathogenically explained at all stages of post stroke rehabilitation. Ethylmethylhydroxypyridine succinate (mexidol) is a derivative of succinic acid with antihypoxic, membrane protective, nootropic, anticonvulsant and sedative action. The majority of researchers confirmed the positive effect of mexidol expressed as the marked regression of neurological deficit and wider opportunities for further early rehabilitation. The results of the randomized double blind multicenter placebo-controlled, parallel-group trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA) were published in 2017. The results of the study showed the best positive dynamics of neurological function recovery in case of timely treatment with mexidol with the following two month therapy. The safety of the long-term use of mexidol was confirmed.
Keywords: stroke, acute period, neuroprotection, succinate, efficacy of treatment, safety of therapy.
A comparative study of the effects of mexidolum and mildronatum on the physical performance of experimental animals
Author:
Т.А. VORONINA, I.G. KAPITSA, Е.А. IVANOVA.
Zakusov Institute of Pharmacology, Moscow, Russia.
Summary:
Objective. To evaluate the effects of mexidolum on physical performance using acute and subchronic administration in experimental animals. Materials and methods. The investigation was carried out using 123 male white outbred mice. The forced swim test was used to assess the effects of the drugs on the physical performance of mice. Results and conclusion. A single intraperitoneal administration of 50 and 100 mg/kg mexidolum and subchronic intraperitoneal administration of 100 mg/kg mexidolum significantly enhances the physical performance of animals in the forced swim test. Subchronic intraperitoneal administration of 100 mg/kg of the comparison drug mildronatum enhances the physical performance of animals, while intraperitoneal administration at a lower dose (50 mg/kg) has no effect. The effect of mexidolum at a dose of 50 and 100 mg/kg is comparable with the effect of mildronatum in a dose of 100 mg/kg.
Keywords: physical performance, mexidolum, mildronatum, mice.
Тhе neuroprotective therapy of outpatient treatment of chronic cerebral ischemia
Author:
S.V. BEREZHNAYA, E.Z. YAKUPOV.
Kazan, Municipal health саrе «City hospital №6»; Kazan State Medical University.
Summary:
Objective. То perform а differential analysis of the efficacy of combination therapy bу the drugs with different modalities (mexidol, aescusan, halidorum) in outpatients with chronic cerebral ischemia (CCI), stages I-III. Material and methods. А study included 50 patients with CCI of atherosclerotic, hypertensive and mixed genesis (stage I-20, stage II-20, stage III-10 patients). In addition to somatic therapy, patients received three courses of mexidol, halidorum and aescusan combination therapy during 6 weeks with а 3 month interval between the courses. The changes in subjective complaints and objective clinical manifestations were evaluated after each course. Results and conclusion. The therapeutic efficacy after durable complex therapy bу repeated courses of antioxidants is supported bу the results of clinical and neurological examinations. Mexidol in the combination with aescusan and halidorum contributed to the improvement of cognitive, adaptive, motor functions of the patients with CCI, stages I and II. То increase treatment efficacy in patients with CCI, stage III, we recommend to use the drugs that improve cognitive functions of the patients.
Keywords: chronic cerebral ischemia, mexidol, combination therapy.
Results of a randomized double blind multicenter placebo-controlled, in parallel groups trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA)
Author:
L.V. STAKHOVSKAYA, N.A. SHAMALOV, D.R. KHASANOVA, E.V. MELNIKOVA, A.S. AGAFIINA, K.V. GOLIKOV, E.I. BOGDANOV, A.A. YAKUPOVA, L.V. ROSHKOVSKAYA, L.V. LUKINYKH, T.M. LOKSHTANOVA, I.E. POVERENNOVA, L.A. SHEPANKEVICH.
Pirogov Russian National Research Medical University, Moscow, Russia; Research Institute of Cerebrovascular Pathology and Stroke of Pirogov Russian National Research Medical University, Moscow, Russia; Interregional Clinical-Diagnostic Center, Kazan, Russia; City Hospital №26, St. Petersburg, Russia; City Hospital №40, St. Petersburg, Russia; City General Hospital №2, St. Petersburg, Russia; Kazan State Medical University, Kazan, Russia; Nikolaev Hospital, St. Petersburg, Russia; Vsevolga Clinical Interregional Hospital, Leningrad Region, Russia; Pirogov City Clinical Hospital №1, Samara, Russia; Seredavin Samara Regional Clinical Hospital, Samara, Russia; Research Institute Experimental and Clinical Medicine, Novosibirsk, Russia.
Summary:
Aim. To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS). Material and methods. A randomized double blind multicenter placebo-controlled, in parallel groups trial included 151 patients (62 men and 89 women) with hemispheric IS. Using a method of simple randomization, 150 patients (62 men and 88 women), aged 40-79 years, were randomized into two groups. Patients of Group I were treated with mexidol: 500 mg/day IV infusion for 10 days, followed by 125 mg tid (375 mg/day) PO for 8 weeks. Patients of Group II received the placebo according to the same scheme. The total duration of patients’ participation in trial ranged from 67 to 71 days. Results. By the end of treatment, the mean score on the modified Rankin scale (mRS) was lower in Group I compared to Group II (p=0.04). In Group I, the decrease in mRS mean score (Visit 1-5) was more prominent (p=0.023), percentage of patients with 0-2 scores by mRS scale (Visit 5) was higher (p=0.039), mean NIHSS score lower (p=0.035) in Visit 5 compared to group II. By the end of treatment, the decrease in mean NIHSS score in patients with diabetes mellitus was more prominent in Group I in comparison with Group II (p=0.038). In Group I, the dynamic of improvement of quality of life was more prominent and started from Visit 2 in general population and subpopulation of patients with diabetes mellitus. The share of patients with no problems with movement in space was higher in Group I (p=0.022). There were no statistically significant differences in frequency of side effects in patients of both groups. Conclusion. It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages.
Keywords: acute disturbances of cerebral circulation, mexidol, ethylmethylhydroxypyridine succinate, efficacy and safety, ischemic stroke, acute period, acute rehabilitation period, EPICA.
The distribution of mexidol in the rat’s brain and its subcellular fractions
Author:
A.V. SHCHULKIN, E.N. YAKUSHEVA, I.V. CHERNYKH.
Pavlov Ryazan State Medical University, Ryazan.
Summary:
Objective: To study the penetration of mexidol through the blood-brain barrier into different brain compartments and cell mitochondria. Material and methods. The study was carried out on adult male Wistar rats using the drug mexidol (“Farmasoft” Russia). The penetration of mexidol into different compartments of the brain (the cortex, cerebellum, thalamus and medulla) and distribution between mitochondrial and cytoplasmic fractions of the cerebral cortex was studied. The concentration of mexidol in blood plasma and brain tissues was measured using HPLC. Results and Conclusion. Mexidol penetrated through the blood-brain barrier into brain compartments of rats with the maximal accumulation in the cortex. In the brain cortex cells, mexidol was identified in the cytoplasmic and mitochondrial fractions.
Keywords: mexidol, pharmacokinetics, blood-brain barrier, cortex, cerebellum, thalamus, medulla, mitochondria, HPLC.
The results of the study of the efficacy and safety of mexidol in patients with chronic cerebral ischemia
Author:
E.I. CHUKANOVA, A.S. CHUKANOVA, KH.I. MAMAYEVA.
Pirogov Russian National Research Medical University, Moscow.
Summary:
Objective. To analyze the efficacy and safety of mexidol and their effect on the dynamics of neurological signs of the disease, emotional status and quality of life in patients with chronic cerebral ischemia (CCI). Material and methods. We studied 45 patients with CCI who received mexidol in dose 500 mg a day during 14 days by introvenal introduction with the following peroral administration in doses 500 mg twice a day during 60 days. A comparison group included 30 patients with CCI matched for age, risk factors and severity of neurological symptoms, who did not receive mexidol. Patients of both groups received standard treatment that included medications needed for the complete correction of the risk factors. Cognitive function (MMSE), movement activity and quality of life (SF-36) were assessed. Results. To the end of the study (74th day), a decrease in the severity of movement disorders, normalization of SF-36 scores and improvement of mean values of screening-assessment of cognitive function were identified in patients of the main group compared to those of the comparison group. Conclusion. The high efficacy and safety of treatment of CCI patients with mexidol using.
Keywords: chronic cerebral ischemia, oxidative stress, movement disorders, depression, quality of life, mexidol.
Contemporary paradigm of rational stroke treatment
Author:
S.A. ZHIVOLUPOV, YU.S. BUTAKOVA, I.N. SAMARTSEV.
Department of nervous diseases of the Military Medical Academy; primary vascular compartment Novodvinsk City Hospital, Saint Petersburg, Russia.
Summary:
Stroke was and remains one of the world’s leading medical and social problems. Nowadays we are watching permanent sometimes cardinal changes in view about etiology, pathogenetic mechanisms and therapy of patients with stroke. In this work there have been elucidated contemporary theoretical and practical aspects of stroke treatment and prophylaxis based on the results of multicenter clinical trials and experience of leading foreign and native specialists. Much attention is devoted to the pharmacotherapy of patients with stroke. It is showed that application of neuroprotective drugs is of great importance, among which antihypoxants with pleiotropic action play a crucial role (mexidol).
Keywords: stroke, therapy, prophylaxis, neuroprotection, antihypoxants, mexidol.
Effect of mexidol on the development of the phenomenon of the neuronal excitotoxicity in vitro
Author:
A.V. SHCHULKIN.
Summary:
Effect of mexidol on the development of the phenomenon of the excitotoxic syndrome in vitro has been studied. Mexidol inhibits in vitro the development of glutamate-induced neurotoxicity, ascorbate-dependent (non-enzymatic) and NADPH2-dependent (enzymatic) iron-induced lipid peroxide oxidation, is able in high concentrations to bind superoxide anion-radical, significantly increases the activity of Se-dependent glutathione peroxidase, decreases the activity of induced NO-synthase and does not impact on the activity of glutathione-SH-transferase, catalase and neuronal NO-synthase. These effects underlie the antioxidant and antihypoxic action of the drug.
Keywords: mexidol, glutamate-induced neurotoxicity, lipid peroxide oxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione-SH-transferase, induced and neuronal NO-synthase.
Possibilities of antioxidant therapy for asthenia and cognitive deficit in elderly patients with chronic brain ischemia
Author:
S.N. DUMA.
Research Institute of Therapy, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk.
Summary:
Aim. To evaluate the effect of the antioxidant mexidol on the oxidant-antioxidant potential of low-density lipoprotein (LDL), asthenic and anxious symptoms, and cognitive function of neurodynamic type in elderly patients with chronic brain ischemia (CBI). Subjects and methods. Thirty women (mean age 66.7 years) with grade 1-2 dyscirculatory encephalopathy (DE) were examined. Trends for asthenic, anxious, and cognitive symptoms of neurodynamic type were estimated using the standard tests (MFI-20, Hamilton Anxiety Rating Scale, Schulte Tables, Wechsler test) on days 1, 15, and 60 of mexidol treatment (for 60 days). LDLs were isolated from blood by heparin precipitation. The baseline level of lipid peroxidation products was determined and the concentrations of fat-soluble antioxidants (α-tocopherol, retinol, β-carotene, and xanthins) were examined in the isolated LDLs on days 1 and 5 of the study. Results. A 60-day mexidol therapy cycle statistically significantly caused a reduction in asthenic and anxious symptoms in elderly patients with CBI and induced positive changes in the symptoms of cognitive neurodynamics. Assessing the specific features of the pharmacodynamics of the antioxidant mexidol used in the elderly patients for 15 days revealed a statistically significant positive effect on the oxidative potential of LDLs as a decreased predisposition to their antioxidative processes in vivo. The drug’s effect in elevating the levels of α-tocopherol and β-carotene was altered insignificantly (without statistically significant changes), which reflects the pharmacodynamic features of the drug in the elderly patients. Conclusion. The 60-day cycle of therapy with the antioxidant mexidol has a positive impact on asthenic and neurotic symptoms in the elderly patients with CBI. Mexidol is well tolerated and safe when used long.
Keywords: asthenia, anxiety, cognitive defect, chronic brain ischemia, elderly age, specific features of antioxidant therapy, mexidol.