Yu. A. Pirogov

Mechanisms of positive effects of transplantation of human placental mesenchymal stem cells on recovery of rats after experimental ischemic stroke.

Mesenchymal stem cells isolated from human placenta and in vitro labeled with fluorescent magnetic microparticles were intravenously injected to rats 2 days after induction of focal cerebral ischemia (endovascular model). According to MRT findings, transplantation of mesenchymal stem cells led to an appreciable reduction of the volume of ischemic focus in the brain. Two or three weeks after transplantation, labeled cells accumulated near and inside the ischemic focus, in the hippocampus, and in the subventricular zone of both hemispheres. Only few human mesenchymal stem cells populating the zone adjacent to the ischemic focus started expressing astroglial and neuronal markers. On the other hand, transplantation of mesenchymal stem cells stimulated proliferation of stem and progenitor cells in the subventricular zone and migration of these cells into the ischemic zone. Positive effects of transplantation of these cells to rats with experimental ischemic stroke are presumably explained by stimulation of proliferation of resident stem and progenitor cells of animal brain and their migration into the ischemic tissue and adjacent areas. Replacement of damaged rat neurons and glial cells by transplanted human cells, if it does take place, is quite negligible.

Comparative evaluation of two methods for studies of experimental focal ischemia: magnetic resonance tomography and triphenyltetrazoleum detection of brain injuries.

The volumes of foci of injuries, evaluated by T2-suspended MRT images and analysis of histological sections stained by triphenyltetrazoleum chloride, were compared on a model of unilateral intravascular blocking of the middle cerebral artery branch. The two methods for evaluation of foci of lesions gave close results, correlating with the severity of neurological deficiency in animals subjected to ischemia, manifesting in behavioral tests.

Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T2) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T1) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g·s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

Antitumor effects of monoclonal antibodies to connexin 43 extracellular fragment in induced low-differentiated glioma.

We studied the effect of intravenous administration of monoclonal antibodies to the second extracellular loop of connexin 43 (MAbE2Cx43) on the dynamics of glioma growth and survival of experimental animals. Morphometric analysis of magnetic resonance imaging data showed that weekly intravenous administration of MAbE2Cx43 in a dose of 5 mg/kg significantly reduced glioma volume starting from day 21 after tumor implantation. By day 29, the mean volume of glioma in the experimental group (therapy with specific antibodies) was 2-fold lower than in controls. Deceleration of glioma growth in rats receiving MAbE2Cx43 was accompanied by a significant prolongation of rat lifespan (according to Kaplan−Meier test) and even led to complete recovery without delayed relapses in 19.23% animals. The mechanism of tumor-suppressing effects of antibodies can be related to inhibition of specific functions of connexin 43 in glioma cells in the peritumoral zone.

Antitumor effects of the combination of magnetohydrodynamic thermochemotherapy and magnetic resonance tomography

Fe3O4 nanoparticles were coated with a layer of citric acid, forming coordination bonds between citrate ions and iron ions. The resulting aqueous citrate ferrite colloid was used as a T2-weighted MRI negative contrasting agent. Sequential i.v. doses of citrate ferrite and Magnevist led to increases in MRI image contrast for 40 h and brightness for 30 min; scanning using a Bruker Biospec BC 70/30 USR biospectrotomograph yielded enhanced MRI images. This enhancement of MRI images was used to monitor oncogenesis during magnetohydrodynamic thermochemotherapy (MT) of mammary adenocarcinoma Ca 755 in female C57Bl/6j mice. Dextran ferrite colloid containing cyclophosphamide was tested as a magnetically directed antitumor agent using MT. Treatment of non-infiltrating tumors of volume ≈ 30 mm3 with six sessions of MT each lasting 30 min at 46°C led to 40% tumor regression and 300% increases in survival time. Treatment of infiltrating tumors of volume ≈ 300 mm3 in the same conditions yielded a 200% increase in survival time.

MRI Morphometry of the Cerebral Ventricles in Patients with Attention Deficit Hyperactivity Disorder

A total of 27 right-handed patients aged 7–30 years with diagnoses of attention deficit hyperactivity disorder were studied using standard MRI scans. Of these, 14 were aged below 13 years. The volumes of the lateral ventricles were measured using T1-weighted MRI images of sagittal sections of the brain to a precision of 3 mm3. External head sizes were also measured to allow ventricle volumes to be normalized. All patients underwent complex neuropsychological investigations. Memory was assessed, along with visual, auditory, tactile, and spatial recognition functions and the motor and speech spheres. Test data were assessed in terms of the severity of impairments associated with one brain structure or another on a tenpoint scale. Assessment points were summed for each hemisphere, for the “first area” (cortical structures), and all structures for statistical analysis. Neuropsychological testing revealed functional impairments predominantly of the frontal areas of the hemispheres, the hippocampus, and the reticular formation. Neuropsychological deficits were least linked with alterations in the postcentral and parietal areas of the cortex. Statistical analysis demonstrated a significant positive correlation between the normalized left lateral ventricle volume and the degree of neuropsychological impairments (r = 0.5127 at p = 0.0063) for the whole study group. The correlation was more marked on comparison of the normalized left ventricular volume and the severity of neuropsychological impairments related to the left hemisphere (r = 0.6303 at p = 0.0004). A relationship was seen between the volume of the intraventricular space and cortical functional impairments (r = 0.5071 at p = 0.0069) in patients less than 13 years old. A relationship between ventricular volume and linear head size was confirmed (r = 0.5759 at p = 0.0017), which was more marked in subjects less than 13 years old (r = 0.6833 at p = 0.01).

Bioferroelectricity and related problems: Hydrogen-bonded ferroelectric-like systems

Abstract Short review of bioferroelectricity and related problems is presented. One of the important cases the hydrogen-bonded systems, are analysed in detail. The proposed model describes the soliton-like dynamics of hydrogen-bonded ferroelectrics with two interacting subsystems (protons and ordered ferroelectric) in the vicinity of phase transition. As a results, the shift of the phase transition point is obtained. The results are compared with experimental data on microwave irradiation of triglycine sulphate.

Study of Phthalocyanine Derivatives as Contrast Agents for Magnetic Resonance Imaging

The work is devoted to study of new prototype contrasting agents for magnetic resonance imaging on a base of manganese and gadolinium sulphophthalocyanines. Candidate complexes were shown to possess the R1 molar relaxivity values comparable or exceeding ones for commercially available clinical contrast agents such as Magnevist. Intravenous administration of aqueous solution of studied complexes resulted in significant enhancement of contrast of C6 glioma imaging under T1-weighted protocol, allowing to consider them as perspective for further development. Near infrared photosensitizers based on nanoparticular forms of phthalocyanine derivatives.

Location of the dipoles of the P1 wave of visual evoked potential in the human brain

Line fragments and their intersections are the basic properties of most objects in the visual world [3]; therefore, their rapid and reliable detection is important for image recognition. It is obvious that identification of lines (properties of the first order) and their intersections (properties of the second order) in images occurs in cats and monkeys already in the primary visual cortex where half of neurons detect the orientation of single lines and the other half of neurons more rapidly and strongly respond to their intersections or branching nodes [11, 12]. There is no information on the location of the mechanism responsible for identifying lines and their intersections in the human brain. Our previous study [1] demonstrated differences in the temporal and amplitude characteristics and regional specificity of the components of visual evoked potentials (EPs) in the human brain after presentation of images consisting of lines and crosses. However, the location of the dipole sources of these EP components has not been studied. Nevertheless, such information is important for assessing more precisely the involvement of different zones of the visual cortex in the identification of image properties. Therefore, we studied threedimensional location of dipole sources of the early component of visual EPs (wave P1) in the spherical and real model of the head in 12 subjects during presentation of images consisting of lines and crosses. The P1 component was selected because, first, it is associated with early stages of the processing of simple image features in the visual cortex, and, second, according to fMRT data, the location of the current dipole of the P1 wave coincides with the activation focus in the visual cortex [4]. METHODS The EEG was recorded in the electrophysiological experiments on 12 healthy subjects using a NeocortexPro 40-channel recording system (Neurobotics, Russia) according to the 10‐10 scheme with a sampling rate of 1000 Hz/channel. The right-ear electrode was used as an indifferent electrode. The upper limit of the frequency band of amplifiers was 100 Hz, the lower limit was 0.1 Hz, and the characteristic slope was 12 dB/octave. The subjects studied sat in a chamber isolated from light with a background illumination of 6 cd/m 2 . The images containing sets of lines or crosslike figures were shown for 100 ms on a monitor in a random order with various intervals [1]. The angular size of the image was 18.8° , and the size of its single element (cross or line) was 0.6° . Each experiment included 50 stimuli of each type. The average optical densities of the stimuli were equalized. A short sound warning was given 1 s before the beginning of the stimulus exposition. The subject focused the gaze at the fixation point in the screen center after the signal and watched the appearing image.

Effect of anesthetics on efficiency of remote ischemic preconditioning

Remote ischemic preconditioning of hind limbs (RIPC) is an effective method for preventing brain injury resulting from ischemia. However, in numerous studies RIPC has been used on the background of administered anesthetics, which also could exhibit neuroprotective properties. Therefore, investigation of the signaling pathways triggered by RIPC and the effect of anesthetics is important. In this study, we explored the effect of anesthetics (chloral hydrate and Zoletil) on the ability of RIPC to protect the brain from injury caused by ischemia and reperfusion. We found that RIPC without anesthesia resulted in statistically significant decrease in neurological deficit 24 h after ischemia, but did not affect the volume of brain injury. Administration of chloral hydrate or Zoletil one day prior to brain ischemia produced a preconditioning effect by their own, decreasing the degree of neurological deficit and lowering the volume of infarct with the use of Zoletil. The protective effects observed after RIPC with chloral hydrate or Zoletil were similar to those observed when only the respective anesthetic was used. RIPC was accompanied by significant increase in the level of brain proteins associated with the induction of ischemic tolerance such as pGSK-3β, BDNF, and HSP70. However, Zoletil did not affect the level of these proteins 24 h after injection, and chloral hydrate caused increase of only pGSK-3β. We conclude that RIPC, chloral hydrate, and Zoletil produce a significant neuroprotective effect, but the simultaneous use of anesthetics with RIPC does not enhance the degree of neuroprotection.