Plasmid-based gene therapy with hepatocyte growth factor stimulates peripheral nerve regeneration after traumatic injury.

Peripheral nerve injury remains a common clinical problem with no satisfactory treatment options. Numerous studies have shown that hepatocyte growth factor (HGF) exerts neurotrophic effect in motor, sensory, and parasympathetic neurons in addition to mitogenic, morphogenic, angiogenic, antiapoptotic, antifibrotic, and anti-inflammatory effect on various tissues and cells. In our study we examined efficacy of gene therapy with HGF-bearing plasmid (pC4W-hHGF) to improve consequences of traumatic nerve injury in mice. Treatment by pC4W-hHGF led to restoration of nerve structure and functional recovery compared to similar parameters in control animals. Compound action potentials (CAP) in experimental groups treated with 100 or 200 µg of pC4W-hHGF demonstrated increased amplitude and latency decrease compared to spontaneous recovery control group. In HGF-treated mice histological analysis showed a three-fold increase in axon number in nerve portion located distal to the lesion site compared to control. Moreover, significant functional recovery of n. peroneus communis triggered by pC4W-hHGF gene therapy was observed using the footprints analysis. Obtained results provide evidence for plasmid-based HGF gene therapy as a potential treatment for traumatic injury of peripheral nerve.

Dynamics of Stability of Orientation Maps Recorded with Optical Imaging.

Orientation selectivity is an important feature of visual cortical neurons. Optical imaging of the visual cortex allows for the generation of maps of orientation selectivity that reflect the activity of large populations of neurons. To estimate the statistical significance of effects of experimental manipulations, evaluation of the stability of cortical maps over time is required. Here, we performed optical imaging recordings of the visual cortex of anesthetized adult cats. Monocular stimulation with moving clockwise square-wave gratings that continuously changed orientation and direction was used as the mapping stimulus. Recordings were repeated at various time intervals, from 15 min to 16 h. Quantification of map stability was performed on a pixel-by-pixel basis using several techniques. Map reproducibility showed clear dynamics over time. The highest degree of stability was seen in maps recorded 15-45 min apart. Averaging across all time intervals and all stimulus orientations revealed a mean shift of 2.2 ±â€¯0.1°. There was a significant tendency for larger shifts to occur at longer time intervals. Shifts between 2.8° (mean ±â€¯2SD) and 5° were observed more frequently at oblique orientations, while shifts greater than 5° appeared more frequently at cardinal orientations. Shifts greater than 5° occurred rarely overall (5.4% of cases) and never exceeded 11°. Shifts of 10-10.6° (0.7%) were seen occasionally at time intervals of more than 4 h. Our findings should be considered when evaluating the potential effect of experimental manipulations on orientation selectivity mapping studies.

[CAT'S VISUAL AREA 18 INTERMODULAR INTERACTIONS DEVELOPMENT UNDER DIFFERENT VISUAL ENVIRONMENT].

Primary visual cortex contains a set of modules, and their postnatal development depends on a combination of internal genetic and external (defined by visual environment) factors. In order to examine a development of intermodular interactions in visual cortex of kittens subjected to rhythmic light stimulation (15 Hz and 50 Hz frequencies, groups RLS-15 and RLS-50), we investigate an intermodular signal correlation by mean of optical imaging technique. Data was compared with control kittens and with kittens reared with no visual experience in total darkness (group DARK). A significant reduction of the intermodular correlation coefficient was obtained in the group RLS-15; the correlation coefficient values in the groups RLS-50 and DARK was not affected. Thus 15 Hz rhythmic light stimulation during sensitive periods of development disrupts an efficacy of intermodular neuronal connections.

[Binocularly co-activation modulate development of functional modular systems in cats visual cortex].

Using optical imaging technique and method for histochemical cytochrome oxidase revealing we investigated in three kitten's groups (two experimental and one control) a rhythmically light stimulation on ontogenetic development of orientation columns and cytochrome oxidase blobs in visual area 18. Experimental animals were stimulated by rhythmical light for 3 hrs or 12 hrs per day respectively. It was first obtained that binocular co-activation per se, not accompanied by strabismus, indeed influences cortical columns formation during critical period. We show an opposite effect of stimulation on two different types of cortical columns, and also revealed that these affects are have retained for at least 2 weeks after stimulation was terminated. It was obtained that duration of rhythmically light stimulation determines a volume of functional and anatomic alterations: alterations revealed were more pronounced in animals stimulated for12 hrs per day.

[Long-term recording of single unit activity and criteria for estimation of stability].

Stable single-unit recording in the brain of vertebrates allows to investigate processes underlying neural plasticity. In applied aspect long-term single-unit recording can be useful for development of invasive brain--computer interface. Here we propose a criterion for identification of neurons that were recorded for more than one day. Based only on the spike forms classification yields ambiguous result. Additional parameters (such as form of interspike interval histogram or certain parameters of that histogram) decreased misclassification probability considerably. Using proposed criterion we were able to identify 82 neurons that were recoded for more than one day. In extreme case activity of one neuron was observed for 94 days.

[Quality of neuronal signal registered in the monkey motor cortex with chronically implanted multiple microwires].

Disconnection of central and peripheral parts of motor system leads to severe forms of disability. However, current research of brain-computer interfaces will solve the problem of rehabilitation of patients with motor disorders in future. Chronic recordings of single-unit activity in specialized areas of cerebral cortex could provide appropriate control signal for effectors with multiple degrees of freedom. In present article we evaluated the quality of chronic single-unit recordings in the primary motor cortex of awake behaving monkeys obtained with bundles of multiple microwires. Action potentials of proper quality were recorded from single units during three months. In some cases up to 7 single units could be extracted on a channel. Recording quality stabilized after 40 days since electrodes were implanted. Ultimately, functionality of multiple electrodes bundle makes it highly usable and reliable instrument for obtaining of control neurophysiologic signal from populations of neurons for brain-computer interfaces.

["Podmoskovie"--health resort institution of the Federal Drug Control Service of the Russian Federation celebrates the 20th anniversary].

The article is dedicated to the 20th anniversary of the Federal government health resort institution of the Federal Drug Control Service of the Russian Federation (FGI "Health resort "Podmoskovie" of the Federal Drug Control Service of the Russian Federation). In this health resort were developed treatment programs for patients with abnormalities of the cardiovascular, respiratory and digestive systems; methods of ultrasonic, laser and magnetic therapy, atmospheric hypoxic, herbal medicine, speleotherapy are employed. Widely used natural healing factors of Ruza district of the Moscow region such as climate therapy, treatment with mineral water group of X type of Smolensk from own wells and balneo-mudtherapy. Over the past 20 years 70 000 patients received an appropriate treatment in this health resort.

[Effect of propofol on functional response of neuronal population in cat primary visual cortex].

The impact of system anesthetic propofol on strength of functional response was investigated in population of primary visual cortex neurons. Elaborated protocol of anesthesia allowed appropriate depth of anesthesia and artifact free experimental data recording. At the start of experiment optical access to the surface of cortex was provided. Propofol was used as main general anesthetic. Control of anesthesia depth was carried out by monitoring of physiological parameters. Effect ofpropofol on functional response was evaluated by intrinsic optical imaging. Stability of neuronal response was estimated during whole experiment and after single injection ofpropofol. It was shown that extended administration ofpropofol do not have negative influence on strength of recorded neuronal signal. At the same time bolus of propofol depresses amplitude of response. Practical recommendations are suggested for conduction of longitudinal neurophysiological experiments using propofol as main anesthetic.

[Comparison of its and orientation tuning dynamics in neurons located in different functional domains of cat's primary visual cortex].

Orientation tuning and its dynamics of cat's primary visual cortex neurons located in pinwheel centers and orientation columns were studied during development of response in time. Functional domains in the Cortex were revealed by intrinsic signal optical imaging on functional and vascular maps of cortex. Both maps were used for precise placement of electrodes during recordings. Orientation tuning dynamic of each neuron was analyzed by temporary slices technique. Several types of neurons were observed in different functional domains: neurons with stable preferred orientation (14.5%); cells with preferred orientation dynamically shifted by 102 +/- 5 degrees (40.8%) and neurons with mixed dynamics type (44.7%). In pinwheel centers neurons with stable preferred orientation are differed from neurons with unstable preferred orientation in their features. In particular, they are showing greater response strength for preferred orientation. In orientation columns neurons with stable tuning are demonstrating larger latent periods for all orientations including preferred and non-preferred in comparison to cells with unstable response dynamics. We observed better detection quality of stable orientation neurons than in unstable preferred orientation neurons. Further coding features of neurons belonging to one functional type but located in different domains were compared. In general, located in pinwheel centers stable neurons have shorter latencies and stronger responses than for the stable cells located in orientation columns. Detection features were similar for this functional type of neurons. Unstable neurons located in different functional domains don't differ from each other in orientation tuning characteristics. Functional significance of neurons with stable and unstable preferred orientation located in pinwheel center and orientation columns in visual information processing are discussed.

Processing of functional maps of the cat visual cortex obtained using intrinsic optical signals.

Functional structures of the primary visual cortex, particularly clearly apparent structures such as orientation columns, are studied by recording the brain's intrinsic optical signals. These reflect changes in local neuron metabolism and cerebral blood flow induced by functional loading. Despite the advantages of this method, mapping of neurons with weak signals can be hindered by noise generated by the global and local components of optical signals associated with physiological processes occurring in the body as well as equipment factors. This generates the need to correct functional optical maps to eliminate noise effects. The present report describes a new method of processing functional maps using approximations to identify and remove the global components of the optical signal and other interference from maps. The results are compared with data obtained by traditional map processing methods.

[Overlapping of optical answers for cross-like figures and oriented bars in the cats primary visual cortex].

For the first time by the optical method the population activity of neurons in cat primary visual cortex was observed simultaneously for detectors participating in analysis of first-order (orientation) and second-order (line intersection) features. The maps for cross-like figures and oriented single bars were compared. The comparative analysis allowed us to estimate the degree of overlapping of the activated regions and parts of cortex that were free from overlap. Overlapping zones provided the evidence for the fact that neuronal detectors for line intersections are located in the same neuronal columns as neurons detecting orientations. Differences were observed between maps for vertically oriented and oblique crosses. Those differences were pronounced not only in topography but also in degree of overlapping of activity zones. This may evidence on different contribution of neurons detecting basic and intermediate orientations.

[Processing of functional maps obtained by intrinsic optical signals from the cat visual cortex].

For the study of primary visual cortex functional structure, particularly its inherent orientation columns, the so-called intrinsic optical signal is often used. Intrinsic signal displays changes of the local neuronal metabolism and brain blood flow, induced by functional load. Apart from the advantages of the technique, the mapping of neuronal groups can be impeded by the noise caused by the global components of optical signal corresponding to the ongoing physiological processes in the organism. Because of that the elimination of global effects becomes crucial. The article presents a new method of processing the functional images that enables revealing of global components of the optical signal via approximation, and deleting them from the original images. The results obtained by using the method under discussion are compared to those obtained via the conventional method.

[The area of the optically activated zones of cat area 17 under stimulation with grids of different orientation].

In acute experiments with 9 anesthetized and immobilized cats, the relative tangential square of the activated cortical columns in area 17 was mapped by the intrinsic optical signal under stimulation with grids of different orientation. We examined the "oblique effect", i.e. the greater representation of neurons tuned to the vertical and horizontal orientations vs. oblique orientations in the primary visual cortex. The square of the activated parts of the cortex was estimated under different threshold criteria (80, 60 and 40% of the maximum). The "oblique effect" was not observed in our study: the areas of activation of the cortical columns did not differ statistically for two basic vs. oblique orientations. Reasons for the difference between the results of electrophysiological and optical mapping are suggested and possible contributions of the experimental protocol (anesthesia) and individual visual experience in different animals' samples to the origin of these differences are discussed.

[Organization of management of and role of clinical prognosis in the childhood oncological service of Russia]. / Organizatsiia upravleniia i rol' klinicheskogo prognozirovaniia v detskoi onkologicheskoi sluzhbe Rossii.

Cancer control service cannot be managed without having a clear idea of trends and changes in the incidence of malignant neoplasms and associated death rates. These studies become a basis for setting up oncological facilities for both children and adults, having an adequate infrastructure (final fund, the profile of units, a list of staff, the volume of work). Pediatric oncological rooms to collect statistics, to make a primary diagnosis, a follow-up, and outpatient chemotherapy in children with malignant neoplasms, and to do methological work with pediatric and non-oncological specialized children's out- and inpatient units have been opened in most administrative, regional, territorial, and republican centers. Notification is much more complete where specialized pediatric oncological rooms (Moscow) register such children. Unfortunately, such rooms are still few and so such ill children are registered by regional and city oncological dispensaries (and, as shown, 50% of the patients are outside registration).

[Clinical manifestations and diagnosis of childhood mediastinal tumors]. / Klinicheskie proiavleniia i diagnostika opukholei sredosteniia v detskom vozraste.

Mediastinal tumors make up as high as 7% of the malignant neoplasms in children and are encountered in all age groups, slightly more commonly in preschool children. Three main groups of common symptoms that are typical of mediastinal tumors are identified. These include 1) symptoms associated with tumor compression of thoracic organs; 2) neurological disorders associated with compression or destruction of ganglionary nodes; 3) general symptoms. Posterior mediastinal tumors are diagnosed by X-ray in 85% of cases. X-ray computed tomography makes it possible to judge of the initial site of a neoplasm, the presence of inclusions, the status of adjacent organs and tissues, the density of a pathological focus. Gallium-67 citrate radionuclide study allows one to make an early differential diagnosis between a solid formation and lymph proliferative disease. The lack of morphological verification of a diagnosis requires the use of transthoracic aspiration biopsy whose diagnostic value enhances when it is made under guidance of ultrasound or X-ray computed tomography.

[Organ-preserving surgical interventions in unilateral nephroblastomas in children]. / Organosokhraniaiushchie khirurgicheskie vmeshatel'stva pri monolateral'nykh nefroblastomakh u detei.

The paper presents data available in the literature and the authors' own findings of organ-preserving treatment of 9 children with unilateral nephroblastoma. It proposes absolute and relative indications for organ-preserving treatment in this pathology.