Rhythmic Photostimulation and the Number of α-Rhythm Dipoles in the Human Brain

The numbers of -rhythm equivalent current dipoles (ECD) arising in the human brain before and during rhythmic photostimulation at the -rhythm frequency was studied in six healthy adult subjects. Dipoles were calculated using a single-dipole model for the whole of the -range and three subranges by solution of inverse equations in a three-layer model of the head obtained by simultaneous use of EEG data and MRI tomograms of the subjects' heads. The number of apparent ECD was significantly associated with rhythmic photostimulation and depended on the phase of the -rhythm wave at which stimulation started and on the type of visual illusion (circle, spiral, grid) appearing during this time. The relationship between these data and the hypothetical wave process scanning the human visual cortex at the frequency of the -rhythm is discussed.     

Linked Activity of Neurons in the Sensorimotor Cortex of the Rabbit in the State of a Defensive Dominant and “Animal Hypnosis”

A cryptic focus of excitation (a dominant focus) was created in the brains of rabbits by threshold stimulation of the left limb with a current at a frequency of 0.5 Hz. After creation of a focus, there were equal probabilities of detecting pairs of neurons whose linked activity was dominated by a 2-sec rhythm in the sensorimotor cortex of both the right and left hemispheres (29.3% and 32.4%, respectively). When animals were placed in “animal hypnosis,” the total proportion of neuron pairs whose activity was dominated by the rhythm created by establishment of the dominant decreased significantly only in the right hemisphere (21%). After exiting the state of animal hypnosis, the proportion of neurons in the cortex of the right hemisphere whose activity was dominated by the 2-sec rhythm increased significantly if the neurons in the pair were close-lying but decreased significantly if the neurons in the pair were mutually distant. No such changes after hypnotization were seen in the cortex of the left hemisphere. In both the right and left hemispheres, dominance of the 2-sec rhythm in the activity of pairs of neurons was seen significantly more frequently when cross-correlation histograms were constructed by analyzing cells in relation to the spike activity of neurons generating spikes of the lowest (right hemisphere) or lowest and intermediate (left hemisphere) amplitude on neurograms of multineuron activity. Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 58, No. 2, pp. 183–193, March–April, 2008.     

On the Morphology of the Synaptic Vesicles of the Axospine Synapses in the Rat Visual Cortex

An electron-microscopoical Observationof the shape and form of the synapticvesicles in the axospine synapses of therat visual cortex fixed with glutaralde-hyde and postfixed with osmium tetro-xide is reported.Each axospine synapse in the visualcortex consists of a presynaptic boutonwith a dendritic spine from which it is     

Unipolar Brush Cells – a New Type of Excitatory Interneuron in the Cerebellar Cortex and Cochlear Nuclei of the Brainstem

Published data and the authors' own studies on the morphology, neurochemical specialization, and spatial organization of unipolar brush neurons (UBN) in the cerebellar cortex and cochlear nuclei of the brainstem are reviewed. UBN represent an exclusive category of excitatory interneurons, with a single dendrite which forms a compact branching with a shape reminiscent of that of a brush in its terminal segment. These cells are characterized by an uneven distribution in the granular layer of the cerebellum, being located mainly in its vestibular zones. UBN synthesize glutamate, calretinin, and metabotropic and ionotropic glutamate receptors. The dendritic brush of UBN form giant synapses with the rosettes of glutamatergic and cholinergic mossy afferent fibers. UBN axons form an intracortical system of mossy fibers which, forming rosettes and glomeruli, make contact with the dendrites of other UBN and granule cells. In the circuits of interneuronal communications, UBN can be regarded as an intermediate component, amplifying the excitatory effects of mossy afferent fibers on granule cells in the cerebellar cortex and cochlear nuclei of the brainstem.     

Clinical and Neurophysiological Effects of the Therapeutic Combination of High-Frequency Rhythmic Transcranial Magnetic Stimulation of the Motor and Frontal Cortex in Parkinson’s Disease

Neuroscience and Behavioral Physiology - Objective. To run a parallel placebo-controlled trial to assess the effects of navigated combined high-frequency rhythmic transcranial magnetic stimulation...     

Intercellular Contact Protein β-Catenin in Neurons of the Habenula of the Rat Brain

Neuroscience and Behavioral Physiology - Studies were performed on frontal brain sections (n = 5) from Wistar rats using immunocytochemical methods. This is the first report on the detection of the...     

“Imprints of Reality” in the Systems Mechanisms of Brain Activity

Pavlov's concepts of the dynamic stereotype – imprints of reality – are developed on the basis of the theory of functional systems. Parameters of reality and especially the results of activity satisfying the leading needs of living organisms are dynamically impressed in the form of molecular engrams in structures of the results-of-actions acceptors involved in the dominant motivation. The dominant motivation plays the leading role in retrieval of previously formed engrams of the results-of-action acceptors in different functional systems. A general theoretical concept of the emotional and verbal forms of consciousness and their close interaction in humans is developed.     

Signals Analysis and Clinical Validation of Blood and Oxygen Data in Human Brain

INTRODUCTION Ithadlongbeenbelievedthatthescatteringandabsorptionofnearinfrared throughhumantissuescanonlyofferthesurfaceinformationoftissues〔1〕,butJob-sis〔2〕foundthatinnerinformationofbraincouldbeacquiredwhennearinfraredare usedtoirradiatebrainin1977.Thistechnologyhasstimulatedresearcherstostudy theactivesofhumanbrainwithscatteringofnearinfraredlightandhasdifferent namesindifferenttimes,likenearinfraredspectrum(NIRS),diffusionoftomogra-phy(DOT)andnearinfraredimaging(NIRI).Recentde…     

Investigation on Genetic Heterogeneity of α-Subunit of the Epithelial Sodium Channel in Rat Renal Cortex

Genotypic variability of αENaC mRNA in adult rat kidney caused by deletion at the 3’-end of α-subunit DNA was studied by real-time PCR using specifi c probes with a fl uorescent dye (TaqMan). It was found that mRNA deletion forms (a and b), products of alternative splicing of aENaC gene, are absent in the cortex of adult rat kidney.     

Dynamics of Changes in Electrical Activity in the Rabbit Cerebral Cortex during Sequential Sessions of “Animal Hypnosis”

The dynamics of changes in individual electrical activity rhythms in the premotor, sensorimotor, and temporal-parietal areas of the cortex in both hemispheres were studied in chronic experiments in rabbits during sequential sessions of “animal hypnosis.” These experiments showed that during the first session of “animal hypnosis,” significant changes in electrical activity occurred only in the premotor area of the cortex of the right hemisphere, where there were increases in spectral power in the delta-1 and delta-2 ranges and decreases in spectral power in other ranges of electrical activity. Subsequent sessions of “animal hypnosis” formed increasing changes in electrical activity, which were particularly marked in cortical areas in the right hemisphere. Significant changes in spectral power in the delta and theta ranges of electrical activity in cortical areas did not arise at the beginning of the hypnotic state, but after 4–6 min. During the third session of “animal hypnosis,” the course of electrical activity in the alpha and beta rhythms in the premotor and sensorimotor areas of the cortex became wave-like in nature.     

Prenatal Development of GABA-Immunoreactive Neurons in Human Striate Cortex

Prenatal development of GABA-immunoreactive (GABA-ir) neurons in the striate cortex (SC) of 9 human fetuses ranging from 14th week to full term newborn have been studied immunocytochemically. The GABA-ir cells appeared in all zones across SC with higher density in marginal zone (MZ), subplate (SP), deep intermediate zone (IZ) and proliferative zone (PZ) in 14 th week fetus. Minor changes occured in 17 th week, the density of GABA-ir cells in PZ declined. The density of     

Pazopanib Inhibits the Activation of PDGFRβ-Expressing Astrocytes in the Brain Metastatic Microenvironment of Breast Cancer Cells

Brain metastases occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. Brain colonization of cancer cells occurs in a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although a neuroinflammatory response has been documented in brain metastasis, its contribution to cancer progression and therapy remains poorly understood. Using an experimental brain metastasis model, we characterized the brain metastatic microenvironment of brain tropic, HER2-transfected MDA-MB-231 human breast carcinoma cells (231-BR-HER2). A previously unidentified subpopulation of metastasis-associated astrocytes expressing phosphorylated platelet-derived growth factor receptor β (at tyrosine 751; p751-PDGFRβ) was identified around perivascular brain micrometastases. p751-PDGFRβ⁺ astrocytes were also identified in human brain metastases from eight craniotomy specimens and in primary cultures of astrocyte-enriched glial cells. Previously, we reported that pazopanib, a multispecific tyrosine kinase inhibitor, prevented the outgrowth of 231-BR-HER2 large brain metastases by 73%. Here, we evaluated the effect of pazopanib on the brain neuroinflammatory microenvironment. Pazopanib treatment resulted in 70% (P = 0.023) decrease of the p751-PDGFRβ⁺ astrocyte population, at the lowest dose of 30 mg/kg, twice daily. Collectively, the data identify a subpopulation of activated astrocytes in the subclinical perivascular stage of brain metastases and show that they are inhibitable by pazopanib, suggesting its potential to prevent the development of brain micrometastases in breast cancer patients.Breast cancer is the second most common cause of brain metastasis after lung cancer, occurring in 10% to 15% of advanced patients and in approximately 30% of autopsies.^1,2 Risk factors for the development of brain metastases include young patient age, large primary tumors, multiple positive lymph nodes, and hormone receptor negativity.³ In addition, the incidence of brain metastasis appears to be increasing because of the introduction of more sensitive diagnostic methods and improved therapies, the latter particularly in patients with HER2-overexpressing metastatic breast cancer.⁴ The standard of care for brain metastases is palliative, and in most cases chemotherapy is ineffective.^5,6 New drugs that are both brain permeable and prevent specific pathogenic mechanisms of the brain metastasis process have been identified in preclinical experiments but await appropriate clinical trials.^7–11The cancer microenvironment is of crucial importance for a complete understanding of the disease^12–15 because it is the interface between cancer cells and pathophysiology of the patient.¹⁶ The brain represents a unique microenvironment for epithelial cancers that remains to be further investigated. Salient features include the blood-brain barrier that surrounds the vasculature and protects the brain from unwanted substances and leukocyte infiltration, and a rich cellular milieu, including neurons, pericytes, and glial cells. Because the brain is critical for both cognitive and physical function, microenvironmental changes during cancer metastasis may adversely affect the patient. A better understanding of the brain microenvironment during metastasis may contribute to development of more effective therapeutics.Relatively little is known about the microenvironment of brain metastases of breast or other cancers. Most of our information comes from experimental models of brain metastasis in which brain tropic lines are introduced into the circulation of mice via the left cardiac ventricle or carotid artery and then colonize the brain over a several-week period.^17–20 In the 231-BR model system, cancer cells extravasate the circulatory system and bind to the surrounding basement membrane through β1 integrin; in this microenvironment, cancer cells move and proliferate along the outside of the blood vessels.²¹ During the subclinical stage of the brain metastasis process, where injury is subtle but consistent, a continuous neuroinflammatory response involves activation of astrocytes and microglia, identified by expression of glial fibrillary acidic protein (GFAP) and F4/80 or CD11b/CD45, respectively.^21–23 This neuroinflammatory response is also observed in clinical samples from resected human brain metastases in which reactive astrocytes and microglia both surround and infiltrate the metastatic lesion, validating experimental observations.²² In coculture experiments, glial cells increased the number of colonies formed in soft agar by 231-BR cells by fivefold,²² and astrocytes also increased cancer cell proliferation and up-regulated the expression of survival genes,^24,25 suggesting mechanistic contributions of microenvironmental cells to brain metastasis.Consistent with what has been reported for other organs, platelet-derived growth factor (PDGF)-B is also a key protective factor in noncancerous brain damage,^26,27 contributing to blood-brain barrier stability, angiogenesis, and vascular remodeling through the activation of PDGF receptor β (PDGFRβ)-expressing brain pericytes and neuroglial progenitor cells.^28,29 During cancer progression PDGFRβ expression has long been associated with tumor-associated stromagenic and angiogenic activities.³⁰ However, its role during brain metastasis development is unknown.In this article, we characterize the neuroinflammatory microenvironment of a breast cancer experimental brain metastasis model system (231-BR cells transfected with HER2; 231-BR-HER2) and identify a novel subpopulation of metastasis-activated astrocytes that express an active (phosphorylated) form of PDGFRβ (p-PDGFRβ). The existence of this novel subset of astrocytes was confirmed in resected specimens of human brain metastasis from five patients with HER-2–overexpressing breast cancer, two patients with lung cancer, and one patient with colorectal cancer. Importantly, we demonstrate that primary cultured human astrocytes expressed (activated) p-PDGFRβ in response to tumor-derived soluble factors. We previously reported that pazopanib, an inhibitor of vascular endothelial growth factor receptors, PDGFRs, c-kit,³¹ and B-Raf^19,32 prevented brain metastasis formation in the 231-BR-HER2 model by 73%, targeting B-Raf activation in the tumor cells.¹⁹ Herein, we show that pazopanib also inhibited the activation of p-PDGFRβ–expressing astrocytes in the experimental brain metastasis model and in tumor-activated astrocytes in vitro. Our results indicate that brain-permeable drugs can target both tumor cells and the neuroinflammatory microenvironment in the brain metastatic process.     

Modulation of Peripheral Opioid Receptors Affects the Concentration of μ-Opioid Receptors in Rat Brain

Radioligand binding assay was used to evaluate characteristics of central μ-opioid receptors after peripheral administration of μ-opioid receptor agonist loperamide and antagonist methylnaloxone. These substances do not cross the blood-brain barrier. Loperamide and methylnaloxone produced opposite effects on the density of μ-opioid receptors in the frontal cortex of rat brain. These data confi rm our hypothesis on reciprocal interactions between central and peripheral compartments of the endogenous opioid system.     

Electrical Stimulation of the Brain in Wilson–Konovalov Hepatocerebral Dystrophy (a neuromorphological and neurophysiological analysis)

Stereotaxic surgery was performed in 27 patients. Complete elimination of or significant reductions in hyperkinesia were obtained in 17 cases; five patients died. There was no correlation between the severity of clinical manifestations of hepatocellular dystrophy and the relatively normal quantitative measures of cortical and subcortical biopotentials, which were produced on a background of microstructural changes affecting neurons in these regions. It is suggested that qualitative significance of these biopotentials is that they carry an excess pathological spike activity resulting in hyperkinesia. This is supported by the fact that hyperkinesia was suppressed after surgical destruction of the ventrolateral nucleus of the thalamus and subthalamic structures.     

The Distribution and Morphological Diversity of GABA-containing Neurons in The Prefrontal Cortex of Human Newborn Baby Infant

The prefrontal cortex of a human fulltermnewborn infant just after accidental deathwas studies by mcans of immunocytochemicaltechnique with antibody directedagainst GABA(Immunonuclear Corp.)and ABC kit(Vector)。GABA-containing neurons were found over alllayers and all were nonpyramidal cells.The1aminar distribution of GABA-containing ne-urons was not even between different layers,density in layeRⅡwas prominently higher thanany other layers,density in layerⅢand layerⅣwas higher than that in layer V andⅥ.The tangentia1 distribution over al1 1ayers was     

Role of the Brain Dopaminergic and Opioid System in the Regulation of “Child’s” (Maternal Bonding) Behavior of Newborn Albino Rats

Administration of D₂ receptor antagonist clebopride in a dose not affecting locomotor activity was followed by a decrease in maternal bonding behavior of 10-day-old and 15-day-old albino rat pups. D₁ receptor antagonist SCH23390 had a stimulatory effect only on the behavior of 10-day-old newborns. Opioid peptide β-casomorphin-7 abolished the effect of clebopride in rat pups of the older age group.