Deep Cerebellar Low-Intensity Focused Ultrasound Stimulation Restores Interhemispheric Balance after Ischemic Stroke in Mice.

Ischemic damage after stroke disrupts the complex balance of inhibitory and excitatory activity within cortical network causing brain functional asymmetry. Cerebellar deep nuclei with its extensive projections to cortical regions could be a prospective target for stimulation to restore inter-hemispheric balance and enhance neural plasticity after stroke. In our study, we repeatedly stimulated the lateral cerebellar nucleus (LCN) by low-intensity focused ultrasound (LIFU) for 3 days to enhance rehabilitation after middle cerebral artery occlusion (MCAO) in a mouse stroke model.

Author Correction: Dentate granule and mossy cells exhibit distinct spatiotemporal responses to local change in a one-dimensional landscape of visual-tactile cues.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dentate granule and mossy cells exhibit distinct spatiotemporal responses to local change in a one-dimensional landscape of visual-tactile cues.

The dentate gyrus (DG) is critical for detecting changes in environments; however, how granule cells (GCs) and mossy cells (MCs), the two excitatory cell types of the DG, respond to small changes in the object layout is unclear. Here, we recorded GCs and MCs, identified by spike feature and optogenetic tagging, as mice ran on a treadmill belt enriched with visual-tactile cues. We observed that fixing a new cue on the belt induced a reconfiguration of GC and MC spatial representations via the emergence, extinction and rate alteration of firing fields.

A neuroprotective brain stimulation for vulnerable cerebellar Purkinje cell after ischemic stroke: a study with low-intensity focused ultrasound.

The role of established contralateral cerebrocerebellar connections on cerebellar injury during stroke has been increasingly revealed in recent years. An extensive number of studies have investigated alteration in inter-hemispheric correlation in order to find brain regions whose responses are specific to restore functional loss and enhance adaptive neural plasticity after stroke. Although, several non-invasive brain stimulation studies have proven their efficacy in the treatment of stroke recovery, finding more effective brain regions that responsible for stroke rehabilitation as well as optimizing neural stimulation protocol are the main goals of further investigations.

[The clinical significance of the lamotrigine pharmacokinetic variability].

Aim: To estimate pharmacokinetic variability of lamotrigine (LTG) and its clinical significance.

Material And Methods: One hundred patients, including 74 women, aged from 18 to 77 years (38.23±14.

Implantation of Chronic Silicon Probes and Recording of Hippocampal Place Cells in an Enriched Treadmill Apparatus.

An important requisite for understanding brain function is the identification of behavior and cell activity correlates. Silicon probes are advanced electrodes for large-scale electrophysiological recording of neuronal activity, but the procedures for their chronic implantation are still underdeveloped. The activity of hippocampal place cells is known to correlate with an animal's position in the environment, but the underlying mechanisms are still unclear.

[Experimental study of the basic pharmacokinetic characteristics of dipeptide carnosine and its efficiency of penetration into brain tissues].

We have used an original chromatography/mass spectrometry technique to study the pharmacokinetics of dipeptide carnosine in C57 Black/6 mice after intra-peritoneal administration of the drug at a dose of 1 g/kg. The basic pharmacokinetic characteristics of carnosine were measured the in the blood and brain. The obtained concentration-time curve has a biexponential character.

Experimental investigation of pharmacodynamics and pharmacokinetics of carbamazepine nanoemulsion.

Anticonvulsant activity and pharmacokinetics of nanoemulsion and unmodified substance of carbamazepine were compared in experiments on mice. Carbamazepine nanoemulsion demonstrated significant anticonvulsant activity and was superior to unmodified substance of carbamazepine against seizures induced by maximum electric shock and picrotoxin. Relative bioavailability of carbamazepine after administration of nanoemulsion was 160% compared to unmodified substance.

[Experimental study of pinostrobine oxime biotransformation].

We have experimentally studied pathways of elimination of an oximized derivative of phytoflavonoid pinostrobine by HPLC/mass spectrometry. Four potential metabolites of pinostrobine oxime have been found and there was an attempt to determine their molecular structures on the basis of their fragmentation under positive electrospray ionization conditions. It is established that pinostrobine oxime is removed from the organism mainly unchanged and also in the form of glucuronated derivative.

[Anticonvulsant effect of dicholine succinate on primary generalized epilepsy model in mice].

The anticonvulsant effect of dicholine succinate (DCS), a neuronal insulin sensitizer, has been studied on two models of primary generalized epilepsy induced by corazole and maximal electroshock (ME) in mice. It has been found that DCS administered intraperitoneally for 7 days in a dose of 10 mg/kg produces a significant anticonvulsant effect on the model of corazole-induced seizures. The drug increases the latency of corazole-induced seizures, changes the character of seizures, and increases lifespan of animals, while not protecting against loss.

[Effect of mexidol on 6beta/free hydroxycortisol ratio. Possibility of CYP3A4 activation].

The influence of mexidol (2-ethyl-6-methyl-3-oxypyridine) after a single peroral administration on the levels of 6beta-hydroxycortisol (6beta-OHC) and free cortisol (FC) in human urine has been evaluated. The 6beta-OHC/FC ratio is increased (approximately 2.96 +/- 0.

[Drug bioavailability improvement by means of nanopharmacology: pharmacokinetics of liposomal drugs].

Modern approaches to increasing the efficiency of liposomal transport of substances are discussed. Examples of creating new nanopharmacological drugs that exceed the pharmacokinetic characteristic of their classical analogs are given.

[Comparative pharmacokinetics of dihydroquercetin in rats upon peroral administration of a parent compound and liposomal flamen D].

The pharmacokinetics of dihydroquercetin (DHQ) in the forms of parent substance and a new liposomal formulation (Flamena D) have been studied in rats upon single peroral administration in a dose of 50 mg/kg. DHQ concentration after enzymatic hydrolysis in the blood plasma was determined by HPLC with UV detection. The elimination half-life of DHQ introduced in the form of Flamena D was about T(1/2) = 1.

[Effect of leucomisine on cell and humoral immunity indices].

The influence of the sesquiterpene lactone leucomisine on the cell and humoral immunity indices has been studied. It is established that the administration of leucomisine in a dose of 10 mg/kg dose stimulates IgM and IgG antibody production.

[Experimental evaluation of the antibacterial and phagocytosis-stimulating properties of leucomisine].

It is experimentally demonstrated that the sesquiterpene lactone leucomisine extracted from Artemisia leucodes exhibits pronounced antibacterial and phagocytosis-stimulating activity.

[HPLC-MS determination of 2-ethyl-6-methyl-3-oxypyridine].

An HPLC-ESI-MS method has been developed for determining 2-ethyl-6-methyl-3-oxypyridine (EMO) in human urine upon peroral administration of this substance in form ofmexidol. Various sample preparation (extraction) procedures were tested and compared for evaluating the recovery and matrix effect. Solid-phase extraction procedure followed by derivation with dansyl chloride is proposed as a method of choice.

Effect of succinic acid and tween-80 on glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine.

We studied the effect of succinic acid on the process of glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine after peroral and intraperitoneal administration in the form of succinate or a base. Since the basic form of 2-ethyl-6-methyl-3-hydroxypyridine is insoluble in water, it was administered in 5% Tween-80. It was necessary to evaluate also the effect of Tween-80 on glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine in different administration routes.

[Correlations of pharmacokinetics and pharmacodynamics of a combined preparation containing pyrrolidone and pyroglutamic acid].

Experiments showed that a new drug composition containing pyrrolidone and pyroglutamic acid exhibits a significant cerebrovascular effect upon peroral administration in rats. The pharmacokinetics of pyrrolidone monitored upon its combined administration with pyroglutamic acid shows that this drug, as a component of the composition, is characterized by a high absolute bioavailability and permeability trough the blood-brain barrier. The presence of pyroglutamic acid slows down the absorption and elimination of pyrrolidone and enhances its distribution in the organs and tissues.

[Investigation of the effects of mexidol in escapable and inescapable emotional stress in inbred BALB/C and C57BL/6 mice].

The effect of mexidol administered in a dose of 100 mg/kg (i.p.) was studied in BALB/C and C57BL/6 mice on various emotional stress models including open field test, elevated plus-maze test, and passive avoidance conditioned reflex.

[Pharmacokinetics of mifepristone and kinetics of chorionic gonadotropin beta-subunit (beta-HCG) and progesterone in plasma of pregnant women during pharmacological interruption of early pregnancy].

Reliable correlations between the parameters of mifepriston pharmacokinetics describing the rate of drug elimination from the blood plasma and the levels of beta-human chorionic gonadotropin (beta-HCG) and progesterone reflecting the state of gestation in females have been established fore the first time. According to these relationships, the half elimination time, the mean retention time, and the plasma clearance of mifepriston can be considered as predictors of the clinical efficacy of this drug for the early pregnancy interruption.

[Characteristics of pyrrolidone pharmacokinetics in rats].

The pharmacokinetics of pyrrolidone in a composition with pyroglutamic acid was studied in white mongrel male rats. The former component exhibits cerebrovascular and neuroprotector activity. Pyrrolidone, detected in the blood plasma and brain for 8 h after peroral and intravenous administration, exhibits a high absolute bioavailability and the ability to penetrate via the blood-brain barrier.

[Harmonization of testing drugs for bioequivalence: problems and possible solutions].

Problems encountered in the testing for bioequivalence of reproduced drugs (generics) are discussed in the parts incompletely resolved in domestic methodological recommendations. There are special cases when such drugs significantly vary in concentration and dosage, contain endogenous substances, exhibit intensive metabolism with a genetically polymorphous component, belong to "long-lived" compounds, and are intended for local administration. Also mentioned are problems related to insufficient sensitivity of analytical methods and some ethical aspects of investigations.

[Pharmacokinetics and efficacy of phenazepam after transdermal and enteral administration in rats].

The concentration of fenazepam in the blood plasma of rats upon application of the transdermal therapeutic system (TTS) fenapercuten was very low, incomparable to the drug concentration (recalculated to equal input doses) upon intravenous or enteral administration. Nevertheless, the TTS exhibited a pronounced anxiolytic and weak sedative action in the absence of any side myorelaxant effect. The agent responsible for adverse side effects (3-hydroxyfenazepam) was not determined in the blood plasma upon the TTS application.

[Relation between mexidol glucuronide conjugation and characteristics of its therapeutic effect in patients with organic lesions in the central nervous system].

The clinico-pharmacological and pharmacokinetic investigation of mexidole administered in patients with organic CNS damage showed for the first time that there is a correlation between intensity of the drug--glucurone conjugation and the parameters of psychopathological symptom expression and the individual patient state estimation before treatment and upon a single administration or a course of mexidole therapy. This correlation allows the clinico-pharmacological effects and the therapeutic efficacy of mexidole to be predicted based on the drug metabolism index.

[Pharmacodynamics and pharmacokinetics of the new specific bradycardic preparation bradizole].

The new drug Bradizol (SM-345), a 2-mercaptobenzimidazole derivative producing a specific bradycardic effect, is quite rapidly eliminated upon intravenous bolus in anaesthetiezed cats. After a combined injection (bolus followed by a 60-min infusion), a constant bradizol concentration in the blood plasma is observed over a time period of 90 min. The bradizol-induced bradycardic effect and the drug concentration in the blood plasma are tightly correlated.