Trace elements in the human central nervous system studied with neutron activation analysis

The central nervous system (CNS) should be especially sensitive to disturbances in trace element concentrations because of its high metabolic rate and low capacity for regeneration. Comparatively few studies have been made on trace elements in the CNS, which prompted us to begin a study of trace elements in four different brain lobes of the CNS, as well as in the spinal cord. Samples were obtained at autopsy and handled carefully in order to avoid contamination. They were freeze-dried and sealed in quartz tubes that were irradiated in a nuclear reactor. A simple chemical separation into six fractions was performed. The gamma spectra for these fractions was registered using a Ge(Li) detector and a computerized multichannel analyzer. Results for the following elements were obtained: Ca, Cd, Co, Cr, Cs, Cu, Fe, Rb, Se, and Zn, as well as for Na and K (not reported). Other elements were also detected in some samples. Using this technique, brain samples from ten patients with Alzheimer’s disease and ten control cases were examined.     

Biotropic effects of geomagnetic storms and their seasonal variations

A substantial effect of geomagnetic storms on human health with a confidential probability P = 0.95 was revealed. The quantitative estimates of the biotropic effect are presented. For example, the frequency of occurrence of bursts exceeding the average number of hospitalized patients with mental and cardiovascular diseases during magnetic storms increases approximately 2 times compared with quiet periods (based on the data on 1983-84). The frequency of occurrence of myocardial infarction, angina pectoris, violation of cardial rhythm, acute violation of brain blood circulation during storms increases 2.1; 1.6; 1.6; 1.5 times, respectively compared with magnetically quiet periods (based on the data of 1992-96). A similarity of the seasonal distribution of the magnitude of the biotropic effect is revealed in the case of myocardial infarction and the number of magnetic storms: a maximum in the equinox and a minimum in summer.     

The spatial structure of the alpha rhythm in the healthy human being studied by EEG mapping]

EEG study was conducted in the state of relative rest in 15 healthy subjects with predominance of the alpha rhythm. Data processing was performed on neuromapper ("Neuroscience", Great Britain). Principal attention was paid to the dynamics of spatial-temporal relations of the alpha rhythm. Cyclic changes were shown of the alpha-rhythm amplitude, proceeding with change of high and low amplitudes during seconds, varying in time in various individuals. Three types of spatial distribution of the alpha rhythm over the cortex at the relative rest were obtained: 1) generalized distribution over the cortex with the wavy shift of the frequency fields; 2) formation of delimited local zones of the alpha rhythm, differing by the frequency from the rhythm in other cortical areas; 3) local zone of the low-frequency alpha rhythm in the visual projection zone (18 and 19 fields). Change of the distribution types of the alpha rhythm in the state of rest takes place in the seconds of time intervals, corresponding, according to the literature data, to the proceeding of elementary mental processes.     

Reorganization of the human central nervous system

The key strategies on which the discovery of the functional organization of the central nervous system (CNS) under physiologic and pathophysiologic conditions have been based included (1) our measurements of phase and frequency coordination between the firings of alpha- and gamma-motoneurons and secondary muscle spindle afferents in the human spinal cord, (2) knowledge on CNS reorganization derived upon the improvement of the functions of the lesioned CNS in our patients in the short-term memory and the long-term memory (reorganization), and (3) the dynamic pattern approach for re-learning rhythmic coordinated behavior. The theory of self-organization and pattern formation in nonequilibrium systems is explicitly related to our measurements of the natural firing patterns of sets of identified single neurons in the human spinal premotor network and re-learned coordinated movements following spinal cord and brain lesions. Therapy induced cell proliferation, and maybe, neurogenesis seem to contribute to the host of structural changes during the process of re-learning of the lesioned CNS. So far, coordinated functions like movements could substantially be improved in every of the more than 100 patients with a CNS lesion by applying coordination dynamic therapy. As suggested by the data of our patients on re-learning, the human CNS seems to have a second integrative strategy for learning, re-learning, storing and recalling, which makes an essential contribution of the functional plasticity following a CNS lesion. A method has been developed by us for the simultaneous recording with wire electrodes of extracellular action potentials from single human afferent and efferent nerve fibres of undamaged sacral nerve roots. A classification scheme of the nerve fibres in the human peripheral nervous system (PNS) could be set up in which the individual classes of nerve fibres are characterized by group conduction velocities and group nerve fibre diameters. Natural impulse patterns of several identified single afferent and efferent nerve fibres (motoneuron axons) were extracted from multi-unit impulse patterns, and human CNS functions could be analyzed under physiologic and pathophysiologic conditions. With our discovery of premotor spinal oscillators it became possible to judge upon CNS neuronal network organization based on the firing patterns of these spinal oscillators and their driving afferents. Since motoneurons fire occasionally for low activation and oscillatory for high activation, the coherent organization of subnetworks to generate macroscopic function is very complex and for the time being, may be best described by the theory of coordination dynamics. Since oscillatory firing has also been observed by us in single motor unit firing patterns measured electromyographically, it seems possible to follow up therapeutic intervention in patients with spinal cord and brain lesions not only based on the activity levels and phases of motor programs during locomotion but also based on the physiologic and pathophysiologic firing patterns and recruitment of spinal oscillators. The improvement of the coordination dynamics of the CNS can be partly measured directly by rhythmicity upon the patient performing rhythmic movements coordinated up to milliseconds. Since rhythmic dynamic, coordinated, stereotyped movements are mainly located in the spinal cord and only little supraspinal drive is necessary to initiate, maintain, and terminate them, rhythmic, dynamic, coordinated movements were used in therapy to enforce reorganization of the lesioned CNS by improving the self-organization and relative coordination of spinal oscillators (and their interactions with occasionally firing motoneurons) which became pathologic in their firing following CNS lesion. Paraparetic, tetraparetic spinal cord and brain-lesioned patients re-learned running and other movements by an oscillator formation and coordination dynamic therapy. Our development in neurorehabilitation is in accordance with those of theoretical and computational neurosciences which deal with the self-organization of neuronal networks. In particular, jumping on a springboard 'in-phase' and in 'anti-phase' to re-learn phase relations of oscillator coupling can be understood in the framework of the Haken-Kelso-Bunz coordination dynamic model. By introducing broken symmetry, intention, learning and spasticity in the landscape of the potential function of the integrated CNS activity, the change in self-organization becomes understandable. Movement patterns re-learned by oscillator formation and coordination dynamic therapy evolve from reorganization and regeneration of the lesioned CNS by cooperative and competitive interplay between intrinsic coordination dynamics, extrinsic therapy related inputs with physiologic re-afferent input, including intention, motivation, supervised learning, interpersonal coordination, and genetic constraints including neurogenesis. (ABSTRACT TRUNCATED)     

Morphometric evaluations of the human nervous system

It is very important to evaluate and accurately understand the various conditions of the human nervous system. In this review article, we introduce several morphometric reports that are proven to be accurate from the view point of various errors (range of tissue shrinkage ratios, microscopic multiple counting, artifacts of microscopic structures, etc.). We review the following aspects of the selected reports: methodology, developmental research, neuronal differences, gender differences, aging process and miscellaneous (nerve fibers, unmyelinated fibers, in relation to neuropathology, clinical image-analysis and immunohistochemistry).     

Modular organization of finger movements by the human central nervous system

The motor system may generate automated movements, such as walking, by combining modular spinal motor synergies. However, it remains unknown whether a modular neuronal architecture is sufficient to generate the unique flexibility of human finger movements, which rely on cortical structures. Here we show that finger movements evoked by transcranial magnetic stimulation (TMS) of the primary motor cortex reproduced distinctive features of the spatial representation of voluntary movements as identified in previous neuroimaging studies, consistent with naturalistic activation of neuronal elements. Principal component analysis revealed that the dimensionality of TMS-evoked movements was low. Principal components extracted from TMS-induced finger movements resembled those derived from end-postures of voluntary movements performed to grasp imagined objects, and a small subset of them was sufficient to reconstruct these movements with remarkable fidelity. The motor system may coordinate even the most dexterous movements by using a modular architecture involving cortical components.     

Biphasic ventilatory response to hypoxia in unanesthetized rats

To determine the role of postinspiratory inspiratory activity of the diaphragm in the biphasic ventilatory response to hypoxia in unanesthetized rats, we examined diaphragmatic activity at its peak (DI), at the end of expiration (DE), and ventilation in adult unanesthetized rats during poikilocapnic hypoxia (10 % O2) sustained for 20 min. Hypoxia induced an initial increase in ventilation followed by a consistent decline. Tidal volume (VT), frequency of breathing (fR), DI and DE at first increased, then VT and DE decreased, while fR and DI remained enhanced. Phasic activation of the diaphragm (DI-DE) increased significantly at 10, 15 and 20 min of hypoxia. These results indicate that 1) the ventilatory response of unanesthetized rats to sustained hypoxia has a typical biphasic character and 2) the increased end-expiratory activity of the diaphragm limits its phasic inspiratory activation, but this increase cannot explain the secondary decline in tidal volume and ventilation.     

On the reactions of the human nervous system to complex-frequency optical stimulation

A computerized system for precise stimulation and analysis of electroencephalographic (EEG) reactions to two simultaneously presented frequencies of sine-wave light (one constant, 13 Hz, and the other varying from 1 to 6 Hz and vice versa) was used to study the mechanisms of human brain reactivity to complex rhythmical stimulation. The frequencies were generated by computer and presented to the subjects by three different ways: as a result of their simple summation (additively), as a product of their multiplication (multiplicatively, amplitude modulation of constant frequency by the varying frequency), or by separate presentation to different eyes. The dynamics of electroencephalograms for different types of stimulation were compared. Under all three experimental conditions, the dynamics of EEG spectra has demonstrated the same general pattern of resonance activation, which was similar to that observed for the presented signals in the case of their amplitude modulation. Significant positive shifts in the functional state of subjects were observed as a result of stimulation. The results obtained show the leading role of the processes of amplitude modulation in the interaction of integrative, adaptive, and trace mechanisms of the brain functioning during human perception of complex rhythmical stimuli.     

Mutations in human lymphocytes studied by an HLA selection system

Human lymphocytes mutated at the HLA-A2 or HLA-A3 alleles were enumerated and studied by primary selection using antibody and complement, followed by limiting dilution cloning and secondary selection using immunofluorescence or antibody and complement. The geometric mean frequency of in vivo mutant lymphocytes was 3.08 X 10(-5) for the HLA-A2 allele and 4.68 X 10(-6) for the HLA-A3 allele. Mutagenesis by X-radiation or mitomycin produced a dose-related increase in mutant frequency. HLA-B phenotyping and Southern Analysis of the HLA-A gene suggested that mutation was frequently due to gene deletion, which was often substantial.     

Biphasic effect of gingipains from Porphyromonas gingivalis on the human complement system

Periodontitis is an inflammatory disease of the supporting structures of the teeth and is caused by, among other agents, Porphyromonas gingivalis. P. gingivalis is very resistant to killing by human complement, which is present in a gingival fluid at 70% of the serum concentration. We found that the incubation of human serum with purified cysteine proteases of P. gingivalis (gingipains) or P. gingivalis wild-type strains W83 and W50 resulted in a drastic decrease of the bactericidal activity of the serum. In contrast, serum treated with P. gingivalis mutants lacking gingipains (particularly strains without HRgpA) maintained significant bactericidal activity. To understand in detail the mechanism by which gingipains destroy the serum bactericidal activity, we investigated the effects of gingipains on the human complement system. We found that all three proteases degraded multiple complement components, with arginine-specific gingipains (HRgpA and RgpB) being more efficient than lysine-specific gingipain (Kgp). Interestingly, all three proteases at certain concentrations were able to activate the C1 complex in serum, which resulted in the deposition of C1q on inert surfaces and on bacteria themselves. It is therefore plausible that P. gingivalis activates complement when present at low numbers, resulting in a local inflammatory reaction and providing the bacteria with a colonization opportunity and nutrients. At later stages of infection the concentration of proteases is high enough to destroy complement factors and thus render the bacteria resistant to the bactericidal activity of complement.     

A role for the enteric nervous system in the response to helminth infections

The enteric nervous system (ENS) in the gut contains a particularly high concentration of nerve cells, and effectively functions as an independent 'minibrain'. Interactions between nerve, endocrine, immune and other cell types allow the sophisticated regulation of normal gut physiology. They can also bring about a co-ordinated response to parasitic infection, possibly leading to expulsion of the parasite. In this review, Derek McKay and Ian Fairweather will consider, in brief, data pertaining to changes in the ENS following intestinal helminth infections and speculate on the role that these alterations may have in the expulsion of the parasite burden and the putative ability of the parasite to modulate these events.     

Antibodies to glycolipids in demyelinating diseases of the human peripheral nervous system

Antibodies to complex glycolipids occur in patients with a variety of diseases of the peripheral nervous system. Many patients with demyelinating neuropathy occurring in association with IgM paraproteinemia have a monoclonal antibody that reacts with a carbohydrate determinant shared between sulfate-3-glucuronyl paragloboside (SGPG), the myelin-associated glycoprotein and other glycoproteins of peripheral nerve. Other patients with neuropathy in association with IgM paraproteinemia have monoclonal antibodies reacting with carbohydrate determinants on various gangliosides. More than 80% of the IgM monoclonal antibodies from patients of this type that have been screened in our laboratory react with SGPG or ganglioside antigens. High levels of antibodies reacting with ganglioside antigens are also found in some patients with inflammatory neuropathies such as Guillain-Barré Syndrome and chronic relapsing inflammatory polyneuropathy. The pathogenetic significance of these antibodies reacting with acidic sphingoglycolipids remains to be established.     

The effects of geomagnetic storms on proteinase and glycosidase activities in fish intestinal mucosa

It has been demonstrated that the glycosidase activity of cyprinoid fishes (carp and crucian carp) exposed to a geomagnetic storm for up to 20 h considerably decreases; however, the proteinase activity is weakly altered (a statistically significant decrease in the enzyme activity has been observed only in fasting fish). An in vitro study of the effects of individual half hour intervals of the geomagnetic storm that correspond to the main and recovery phases on the same enzyme activities demonstrates the opposite trend. Independently of the experimental conditions, geomagnetic storms have been shown to influence the enzyme system of fasting fish negatively.     

The DNA double-strand break response in the nervous system

DNA double-strand breaks (DSBs) require a coordinated molecular response to ensure cellular or organism survival. Many factors required for the DSB response, including those involved in non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are essential during nervous system development. Additionally, human syndromes resulting from defective responses to DNA damage often feature overt neuropathology such as neurodegeneration. Thus, appropriate responses to DSBs are critical for the normal development and maintenance of the nervous system.