[A systematic analysis of neurobiological roles of lithium]. / Neirobiologicheskaya rol' solei litiya.

Lithium salts have been the mainstay of treatment for bipolar disorder for more than 50 years, since the FDA approved the treatment in 1970. Molecular mechanisms of lithium's action include inhibition of glycogen synthase kinase 3 beta and inositol monophosphatase, resulting in induction of brain-derived neurotrophic factor, antiapoptotic proteins, deprivation of calcium-induced apoptosis. Recent findings suggest autophagy regulation as a possible mechanism of lithium neuroprotective action. Moreover, lithium treatment has been reported to decrease accumulation of various pathological proteins including phosphorylated tau and amyloid-B. Also, telomeres length and telomerase activity are suggested to be upregulated by lithium. Clinical applications of lithium treatment include various neurodegenerative diseases, primarily Alzheimer disease, with increasing importance given to the use of lithium microdoses. Chemoreactome screening is used to find more safe and effective lithium compounds.

[Deficit of Magnesium and States of Hypercoagulation: Intellectual Analysis of Data Obtained From a Sample of Patients Aged 18-50 years From Medical and Preventive Facilities in Russia].

The states characterized by pronounced hypercoagulable components (deep vein thrombosis, cardio- and cerebro-vascular pathologies) are caused by multiple pathophysiological factors, including insufficient supply of magnesium (Mg) and other micronutrients. AIM: to present results of analysis of the Institute of Microelements Data Base (IMDB) performed from point of view of interrelationships of Mg deficit and hypercoagulable states in adults treated in medico-preventive facilities of Central, Northwestern, Northern, and Siberian federal districts of Russia. METHODS: The analysis was realized as analysis of data obtained in a cross-sectional study. In the cohort of patients (n=1453) formed from the IMBD adequacy of Mg supply was assessed by magnesium levels in blood plasma (Mg BP) (0.69±0.15 mmol/L) and estimates of daily Mg consumption according to dietary diaries (Mg D) (185±90 mg/day). RESULTS: Mg supply was adequate (Mg BP >0.80 mmol/L, Mg D >300 mg/day) in not more than 6 % of patients. Presence of "Hypercoagulation" label in data base was associated with greater number of chronic diseases (2.3±2.1 and 0.83±0.8 with and without this label, respectively, р=0.0006) and elevated risk of the presence on 4 comorbid pathologies (odds ratio [OR] 18, 95 % confidence interval [CI] 10-25, р=0.0006). Mg deficit (Mg BP.

Deficit of Magnesium and States of Hypercoagulation: Intellectual Analysis of Data Obtained From a Sample of Patients Aged 18-50 years From Medical and Preventive Facilities in Russia.

The states characterized by pronounced hypercoagulable components (deep vein thrombosis, cardio- and cerebro-vascular pathologies) are caused by multiple pathophysiological factors, including insufficient supply of magnesium (Mg) and other micronutrients. AIM: to present results of analysis of the Institute of Microelements Data Base (IMDB) performed from point of view of interrelationships of Mg deficit and hypercoagulable states in adults treated in medico-preventive facilities of Central, Northwestern, Northern, and Siberian federal districts of Russia. METHODS: The analysis was realized as analysis of data obtained in a cross-sectional study. In the cohort of patients (n=1453) formed from the IMBD adequacy of Mg supply was assessed by magnesium levels in blood plasma (MgBP) (0.69±0.15 mmol/L) and estimates of daily Mg consumption according to dietary diaries (MgD) (185±90 mg/day). RESULTS: Mg supply was adequate (MgBP >0.80 mmol/L, MgD >300 mg/day) in not more than 6% of patients. Presence of "Hypercoagulation" label in data base was associated with greater number of chronic diseases (2.3±2.1 and 0.83±0.8 with and without this label, respectively, р=0.0006) and elevated risk of the presence on 4 comorbid pathologies (odds ratio [OR] 18, 95% confidence interval [CI] 10-25, р=0.0006). Mg deficit (MgBP.

[A study of the neuroprotective effect of mexidol on the cell model of glutamate stress]. / Izuchenie neiroprotektivnogo deistviia meksidola nakletochnoi modeli glutamatnogo stressa.

AIM: To study a neuroprotective effect of mexidol on the cell model of glutamate stress. MATERIAL AND METHODS: Cytological studies of an effect of glutamate stress on cerebellar granule cells were carried out. RESULTS: Mexidol increased neuronal survival after the addition of glutamate by 8-10% (p<0.05). The effect of mexidol was more pronounced at the stage of neuron culture growth (5 days), cell survivability increased on average by 20%. CONCLUSION: The results of the study confirmed the neuroprotective effect of mexidol in the neuronal culture in glutamate toxicity model.

[An experimental study of anticonvulsant effects of myo-inositol and folic acid]. / Protivosudorozhnye effekty mio-inozitola v sochetanii s folievoi kislotoi v eksperimente.

AIM: To study the micronutrients that potentiate the action of anticonvulsant drugs, and in particular, of myo-inositol (vitamin B8). MATERIAL AND METHODS: An experimental study of neurotrophic and anticonvulsant effects of a preparation based on myo-inositol (inofert) on thiosemicarbazide models of seizures was carried out. RESULTS: Inofert significantly increased the latent time before the first convulsive seizure, reduced the severity of seizures (p<0.05) and reduced mortality in the models of thiosemicarbazide seizures. Myo-inositol enhanced anticonvulsant action of gabapentin and sodium valproate; neuroprotective effect of myo-inositol was also confirmed. CONCLUSION: The Inofert preparation, containing myo-inositol and folic acid, modulates the effects of drugs with both convulsive and anticonvulsive action, reduces the severity and duration of seizures caused by thiosemicarbazide and increases the survival rate of animals.

[Neurotrophic effects of lithium stimulate the reduction of ischemic and neurodegenerative brain damage].

For over 60 years, high doses of lithium (hundreds of milligrams of elemental lithium) have being used to treat bipolar disorder. However, only during the past 20 years the relevant basic and clinical studies have shown that neuroprotective and neurotrophic effects of lithium are possible in much smaller doses ( hundreds of micrograms of elemental lithium). These data indicate a significant potential for the clinical applications of lithium-based drugs in modern neurology for the purposes of prevention and treatment of neurodegenerative and ischemic pathologies. Pharmacological and molecular biology studies indicated that the inhibition of glycogen synthase kinase-syntentase-3 (GSK-3) and induction of brain-derived neurotrophic factors are the main mechanisms of neurotropic actions of lithium. Also, by inhibiting the NMDA receptors, lithium regulates the calcium homeostasis and inhibits the activation of calcium-dependent apotosis. These and other molecular mechanisms of lithium action protect neurons from ischemia and neurodegeneration thus contributing to a significant reduction of neurological deficit in various models of stroke and neurodegenerative diseases.

[Evaluation of the antitumor potential of cerebrolysin]. / Otsenka protivoopukholevogo potentsiala tserebrolizina.

AIM: To investigate the effect of cerebrolysin on the growth and metastasis of malignant tumors in mice (a model of lung carcinoma Lewis). MATERIAL AND METHODS: The study was performed on 60 male mice, hybrids F1 (the age of 2-2.5 months, body weight 19-22g.). Transplantable epidermoid Lewis lung carcinoma (LLC) was used as a standard experimental model to evaluate the properties of the potential antitumor agents. Experimental animals were administered a single intraperitoneal injection of cerebrolysin in doses of 524 mg/kg (n=20) and 1800 mg/kg (n=20) daily from 2 to 16 days after tumor transplantation. RESULTS AND CONCLUSION: Compared with the control group (n=20), cerebrolysin induced growth inhibition of LLC during the treatment (7 to 16 days). An impact of the drug was accompanied by the inhibition of the tumor growth rate by 10-15% (p<0.05). Cerebrolysin demonstrated a dose-dependent effect of reducing the large number of metastases: a number of large metastases significantly decreased by 30-50% with the increase of cerebrolysin dose (p=0.01). Cerebrolysin can significantly suppress the growth rate of Lewis lung carcinoma.

[Pharmacokinetic and pharmacodynamic synergism between neuropeptides and lithium in the neurotrophic and neuroprotective action of cerebrolysin].

OBJECTIVE: To study the synergism between neuropeptides and lithium ions. MATERIAL AND METHODS: An experimental model of stroke (chronic bilateral occlusion of the common carotid arteries in rats), neuronal culture studies, histomorphological analyses, determination of micronutrient profile of brain substrates were used. RESULTS: A complex of experimental studies revealed that the effect of cerebrolysin is influenced by the synergism between lithium ions and the neuropeptide contentof this drug. Pharmacokinetic synergism promotes the accumulation of lithium in brain tissues during cerebrolysin treatment. The existence of the pharmacokinetic synergism is evident from the potentiation of neuroprotective effects of the drug under the action of lithium ions established in the model of stroke. CONCLUSION: Lithium ions potentiate neuroprotective effects of cerebrolysin.

[Mechanisms of neurotrophic and neuroprotective effects of cerebrolysin in cerebral ischemia]. / Mekhanizmy neirotroficheskogo i neiroprotektornogo deistviia preparata tserebrolizin pri ishemii golovnogo mozga.

Cerebrolysin is the drug which contains peptides derived from the brain of a pig. It is used in neurological practice for recovery of stroke patients and treatment of dementia. Despite the evidence-basis and some experimental studies, the distinct mechanisms of pharmacological action of this drug remain unclear for most neurologists. In this paper, we present results of a molecular-biological analysis of peptide content of cerebrolysin. We have demonstrated the presence of active peptide fragments of nerve growth factor, enkephalins, orexin, halanin. The results of current clinical and experimental studies of cerebrolysin have been compared. The activity of above-mentioned neuropeptides explain experimental and clinical details of all known effects (neurotrophic, neuroprotective and immunomodulating) of cerebrolysin in ischemic and neurodegenerative CNS injuries. The analysis allowed to make conclusions about mechanisms of cerebrolysin action that were important for increasing the efficacy of this drug in clinical practice.

[Neurobiology of lithium].

In addition to well-documented mood-stabilizing effects, lithium can be used in the treatment of acute brain injuries (ischemia) and chronic (neurodegenerative) diseases. Recent in vitro and in vivo studies reveal that the long-term treatment with lithium up-regulates cell survival molecules (Bcl-2, cAMP-responsive element binding protein, GRP 78, brain-derived neurotrophic factor, Hsp70) and down-regulates pro-apoptotic activities (e.g., excitotoxicity, p53, Bax, caspase, cytochrome C release, beta-amyloid peptide production and tau hyperphosphorylation) thus preventing or even reversing the neuronal cell death and neurogenesis retardation.