Development of motor and emotional disorders in rats during daily administration of subliminal doses of picrotoxin

It was shown in the experiments on rats, that three neuropathological syndromes develop as a result of daily subthreshold picrotoxin injections (1.25 mg/kg). Maximal expression of syndromes was different during various periods of kindling. The development of seizure syndrome was followed by prevalence of enhanced electrical activity in hippocampus; the development of "akinetic" syndrome was the same in the caudate nuclei. Data are discussed on the positions of theory of the generator, determinant and systemic mechanisms of neuropathological syndromes.     

Prolongation of sleep following creation of a generator of pathologically enhanced excitation in the orbital cortex

Acute experiments on cats showed that injection of tetanus toxin into the orbital cortex (which destroys various types of inhibition) resulted in the formation of a local generator of pathologically enhanced excitation in this cortex area. Chronic experiments showed that cats with such a generator in the orbital cortex developed pathological changes of sleep, expressed in reduction of the duration of wakefulness and development of the slow-wave and paradoxical sleep phases being, retained. The results of this investigation confirm the view on the participation of the orbitofrontal cortex in sleep induction. They are in favour of the general conception on the role of the determinant structure in the nervous system activity and the theory of the generator mechanisms of the neuropathological syndromes characterized by the hyperactivity of the system.     

Effect of electric stimulation of the caudate nucleus on the foci of epileptic activity in the cerebral cortex

It was shown in the acute experiments on rats that caudate nucleus is one of the main structures of brain antiepileptic system. It was noted that reduction of the influence of activating cerebral structures is a tool for abolishing the proepileptic effects which occur in some cases under conditions of electrical stimulations of neostriatum. Results of the investigation confirm G. N. Kryzhanovsky theory of a role of system-antisystem interrelations in suppression of neuropathological syndromes as a result of system hyperactivity.     

Mitochondrial regulation of local supply of energy in neurons

Brain computation is metabolically expensive and requires the supply of significant amounts of energy. Mitochondria are highly specialized organelles whose main function is to generate cellular energy. Due to their complex morphologies, neurons are especially dependent on a set of tools necessary to regulate mitochondrial function locally in order to match energy provision with local demands. By regulating mitochondrial transport, neurons control the local availability of mitochondrial mass in response to changes in synaptic activity. Neurons also modulate mitochondrial dynamics locally to adjust metabolic efficiency with energetic demand. Additionally, neurons remove inefficient mitochondria through mitophagy. Neurons coordinate these processes through signalling pathways that couple energetic expenditure with energy availability. When these mechanisms fail, neurons can no longer support brain function giving rise to neuropathological states like metabolic syndromes or neurodegeneration.     

Role of the Right- and Left-Hemispheric Structures in Speech and Memory Formation in Children

The role of structures of the left and right cerebral hemispheres in formation of speech function and memory was studied on the basis of complex examination of children with developmental speech disorders. On the basis of EEG estimation of the functional state of the brain, children were classified in two groups depending on the side of localization of changes in electrical activity: those with local changes in electrical activity in the left hemisphere (group I) and those with changes in the right hemisphere (group II). The medical history suggested that the observed features of topography of local changes in electrical activity were linked with the character of prenatal and labor complications and their consequences leading to embryo- and ontogenetic disorders in development of different brain regions. Comparison of the results of neuropsychological examination of the two groups showed that different regions of the brain cortex of both the left and right hemispheres are involved in speech formation. However, a specific role of the right hemisphere in formation and actualization of automatic speech series was revealed. It was suggested that the integrity of gnostic functions of the right hemisphere and, primarily, the spatial organization of perception and movements is a necessary factor of development of auditory–speech and nominative memory.     

Improved fixation and cobalt-glucose oxidase-diaminobenzidine intensification for immunohistochemical demonstration of corticotropin-releasing factor in rat brain

An optimal fixation method and intensification procedure may be required in brain immunohistochemistry to obtain intense and widespread staining for a specific antigen, in cases where ordinary fixation and conventional immunohistochemistry result in only partial demonstration of the antigen. In the present study of localization of corticotropin-releasing factor immunoreactivity (CRFI) in rat brain, the importance of such intensification is shown. We describe a fixation procedure in which perfusion of rat brain with Bouin's solution is followed by a PBS wash and a further perfusion with either Zamboni's fluid or 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4), for subsequent investigation of the detailed localization of CRFI in cerebral cortex and subcortical structures. The cobalt-glucose oxidase-diaminobenzidine (Co-GOD) intensification method has been modified to increase the sensitivity of immunostaining by reducing the concentration of glucose oxidase, which is added to the final incubation solution as a generator of hydrogen peroxide. The use of cobalt acetate instead of cobalt chloride appears to slightly suppress background staining in the Co-GOD method. Combination of the two modified procedures was applied to visualize intense and widespread CRFI in a variety of rat brain regions, including median eminence, cerebral cortex, and central amygdaloid nucleus.     

Stereotactic brain biopsies in presenile dementia

Early detection and precise diagnosis of presenile dementias are important since they determine subsequent medical care. Presently the only way to classify these syndromes is by neuropathological examination. Between 1972 and 1987, 222 stereotactic serial brain biopsies were performed in 25 selected demented patients. Comparison between preoperative clinical diagnosis and histological finding gives the following results: in 32% the clinical diagnosis has been confirmed, in 60% the diagnosis has been corrected or specified and in 8% the stereotactic brain biopsies only showed unspecific pathological gliosis.     

Receptor Plasticity in the Human Brain: Some Autoradiographic Studies

Abstract

Receptor modifications in human posmortem material were studied by quantitative autoradiography. Alterations of several neurotransmitter receptors in neurodegenerative diseases such as senile dementia and Huntington's chorea, in lesions of specific brain pathways, like the visual pathway or after drug treatments, were examined. In all these situations alterions of the density or localization of receptors were seen using autoradiography. The results suggest that several mechanisms of receptor adaptation operate in the human brain. These mechanisms include: 1) compensatory changes in receptor density as a consequence of cell loss, in some cases preceding the neuropathological changes; 2) differential alterations in receptors depending on their location in a given pathway, for example in the visual pathway or 3) selective homologous or heterologous modification of receptors after drug treatment.     

Early SIV encephalopathy

SIV encephalopathy was studied in rhesus macaques early after intracerebral (IC) or intravenous (IV) inoculation. Although SIV was detected in the brain of all IC-inoculated animals, the CNS showed moderate neuropathological changes. IV-inoculated animals presented a spectrum of brain changes ranging from perivascular infiltrates to multinucleated giant cells. CNS infection was detected as early as seven days post-IV-inoculation, mostly in a perivascular localization. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express macrophage markers.     

Stereographic reconstruction of human brain CT series

A relatively simple method for the three-dimensional reconstruction of brain contours from a series of CT scans is presented. A procedure is described for storing the structural information obtained from the CT series and for organizing and displaying the data. Furthermore, it is shown how additional features such as standardized artery information taken from an atlas can be superimposed on the spatially reconstructed brain model. It is proposed that three-dimensional representations in the form of computed stereo pairs are quite suitable for morphological documentation of specific neuropsychological issues, such as the localization of aphasic syndromes.     

Metabolic profiling and cytological analysis of proanthocyanidins in immature seeds of Arabidopsis thaliana flavonoid accumulation mutants

Arabidopsis TRANSPARENT TESTA19 (TT19) encodes a glutathione‐S‐transferase (GST)‐like protein that is involved in the accumulation of proanthocyanidins (PAs) in the seed coat. PA accumulation sites in tt19 immature seeds were observed as small vacuolar‐like structures, whereas those in tt12, a mutant of the tonoplast‐bound transporter of PAs, and tt12 tt19 were observed at peripheral regions of small vacuoles. We found that tt19 immature seeds had small spherical structures showing unique thick morphology by differential interference contrast microscopy. The distribution pattern of the thick structures overlapped the location of PA accumulation sites, and the thick structures were outlined with GFP‐TT12 proteins in tt19. PA analysis showed higher (eightfold) levels of solvent‐insoluble PAs in tt19 immature seeds compared with the wild type. Metabolic profiling of the solvent‐soluble fraction by LC‐MS demonstrated that PA derivatives such as epicatechins and epicatechin oligomers, although highly accumulated in the wild type, were absent in tt19. We also revealed that tt12 specifically accumulated glycosylated epicatechins, the putative transport substrates for TT12. tt12 tt19 showed a similar metabolic profile to tt19. Given the cytosolic localization of functional GFP‐TT19 proteins, our results suggest that TT19, which acts prior to TT12, functions in the cytosol to maintain the regular accumulation of PA precursors, such as epicatechin and glycosylated epicatechin, in the vacuole. The PA pathway in the Arabidopsis seed coat is discussed in relation to the subcellular localization of PA metabolites.     

Slow wave and rem sleep mechanisms are differently altered in hereditary pick disease associated with the TAU G389R mutation

Sleep disturbances are found in the course of most dementing syndromes. We report a longitudinal polysomnographic and 18FDG-PET study in a 38-year-old male with FTDP17 carrying the Tau gene mutation G389R. All-night sleep EEG and wake cerebral glucose metabolism at rest (eyes/ears covered) of the preceding day were studied twice, eight months (Night 1; PET 1) and sixteen months (Night 2; PET 2) after the initial neurological evaluation. The Night 1 study showed sleep fragmentation associated to a short REM latency and a severe reduction of slow wave sleep, with relatively preserved NREM-REM sleep cycles; daytime PET 1 revealed severe cerebral glucose metabolic reductions in frontal and temporal areas, with relative preservation of remaining cortical regions and subcortical structures. On Night 2, the total sleep time was less than 5 hours, delta sleep and REM latency remained shortened and only two sleep cycles could be identified; daytime PET 2 exam revealed a greater cortical metabolic impairment and an involvement of subcortical brain regions as compared to PET 1. Post-mortem neuropathological data showed severe neuronal loss, spongiosis and gliosis that were mostly marked in cortical layers I, II, V and VI. In vivo, neurometabolic and post-mortem neuropathological data are consistent with and indicative of a severe dysfunction of intra- and trans-hemispheric regional connectivity and of cortico-thalamic circuits. These findings suggest that the decreased cortical and subcortical connectivity may have been the main pathophysiological mechanism responsible for delta sleep reduction and the cognitive decline.     

Neuro-pathophysiologic effects during primary hyperactivation of the bed nucleus of the stria terminalis in the rat brain

Penicillin administration into the bed nucleus of stria terminalis (BNST) in the rat brain caused epileptiform activity (EpA)--the formation of the generator of pathologically enhanced excitation (GPEE) in the nucleus. GPEE was registered during the first 3 days. EpA was also detected in the amygdala during 5-8 days, and in the hippocamp during the whole period of registration (2-3 weeks). There was the generalized enhancement of synchronized EpA in the range of 6-10 oscillations per s., in some cases with high-amplitude spindle (7-8 oscillations per s.). 50% of animals had emotional behavioural disorders, a marked fear reaction was observed for a month and more. Some animals demonstrated psychotic-like paroxysms with the elements of stereotypy accompanied by high-frequency low-amplitude EpA. It is suggested that when a primary GPEE in BNST is formed, the structures of septo-hippocampal system (BNST, amygdala, hippocamp) play a role of pathological determinants under the influence of which the pathological system consisting of a number of limbic and extrapyramidal structures is formed. Its activity is clinically manifested in the complex polymorphic neuropathological syndrome.     

CEREBRAL PALSY—The Correlation of Clinical and Pathological Observations

Although the causes of cerebral palsy are well known, it is often difficult to assign a cause in specific cases. In some cases, the cause may have been determined on the basis of the history and findings, only to be found in error at autopsy.In four of the five cases of cerebral palsy reported herein, there was correlation between the clinical findings and the neuropathological findings. In the fifth case, before the patient died, the cause of brain damage was thought to be measles encephalitis; but neuropathological evaluation at autopsy indicated that the brain was microcephalic and inadequately developed as a result of genetic factors.     

The multifactor method of EEG separation into the cortical and deep components

A new method of separation of multichannel brain electrical activity into cortical and subcortical components with the help of multifactor analysis is proposed. The method provides a means for isolation and, consequently, more reliable localization of sources of electrical activity not only in deep brain structures (on the basis of the dipole model) but also on the cortical surface. The proposed method does not depend on the rotation and interpretation of factors, and no data losses occur. The mufasel algorithm is based on integration of all selected factors (within a particular EEG or EP time segment) in two groups using a statistical criterion, which defines general and specific factors. It is assumed that general factors loaded with highly correlated derivations predominantly describe the electrical activity of deep brain structures, whereas specific factors loaded by the dynamics of electrical activity in individual derivations, reflect the integrated activity of cortical brain structures.     

Neuroinflammatory implications of Schistosoma mansoni infection: new information from the mouse model

Schistosoma mansoni infection is known to induce granulomas, not only in the liver and intestine, but also in the brain, resulting in neuropathological and psychiatric disorders. In the past, the interaction between Schistosoma mansoni infection and the nervous system has received little attention. Here, Luigi Aloe and Marco Fiore discuss recent findings from experimental Schistosoma mansoni infection in the mouse nervous system showing that brain granulomas are associated with a significant alteration in the constitutive expression of nerve growth factor, a neurotrophic factor that plays an essential role in growth and differentiation and in preventing neuronal damage. These findings suggest that the neuropathological dysfunctions in neuroschistosomiasis may be linked to changes in the basal levels and/or activity of neurotrophic factors caused by local formation of granulomas.     

Dipole tracing of visual evoked potentials in human brain

3D tracing of equivalent current dipoles (ECDs) of averaged human visual evoked potentials (VEP) by their distribution across a 34-electrode array was obtained under short presentation of pattern-onset stimuli (sets of 45 horizontal, vertical bars or crosses). Using a 2-dipole spherical three-layer model, we dynamically (step of 1 ms) localized dipoles in four healthy subjects. Dipole locations were matched to anatomical brain regions visualized in structural MRI. Best-fitting source parameters were superimposed on MR images of each subject to identify the anatomical structures giving rise to the surface patterns. It was found that during 50-300 ms following the onset of the stimuli, the ECDs in all subjects were localized in the occipital cortex and demonstrated reliable systematic shift in localization. Two local (1-2 cm3) zones of the preferable dipole attendance were found at 5-6 cm behind zero line: the first one was localized near the midline of the brain, whereas the other zone was situated in the right hemisphere at a distance of 6-7 cm from the first zone. Their localization and strength of activation were reliably different for crosses and lines and changed during VEP generation. Zones of relatively rare dipole attendance were found also. The data are discussed in relation to localization of initial and endpoint of ECDs trajectories, as well as with sensitivity of the visual cortex to line crossing and branching.     

Effects of the Neurogranin Variant rs12807809 on Thalamocortical Morphology in Schizophrenia

Although the genome wide supported psychosis susceptibility neurogranin (NRGN) gene is expressed in human brains, it is unclear how it impacts brain morphology in schizophrenia. We investigated the influence of NRGN rs12807809 on cortical thickness, subcortical volumes and shapes in patients with schizophrenia. One hundred and fifty six subjects (91 patients with schizophrenia and 65 healthy controls) underwent structural MRI scans and their blood samples were genotyped. A brain mapping algorithm, large deformation diffeomorphic metric mapping, was used to perform group analysis of subcortical shapes and cortical thickness. Patients with risk TT genotype were associated with widespread cortical thinning involving frontal, parietal and temporal cortices compared with controls with TT genotype. No volumetric difference in subcortical structures (hippocampus, thalamus, amygdala, basal ganglia) was observed between risk TT genotype in patients and controls. However, patients with risk TT genotype were associated with thalamic shape abnormalities involving regions related to pulvinar and medial dorsal nuclei. Our results revealed the influence of the NRGN gene on thalamocortical morphology in schizophrenia involving widespread cortical thinning and thalamic shape abnormalities. These findings help to clarify underlying NRGN mediated pathophysiological mechanisms involving cortical-subcortical brain networks in schizophrenia.     

Contribution of magnetic resonance imaging to the knowledge of CNS malformations related to chromosomal aberrations

Summary Twelve patients presenting with various clinicopathological syndromes related to chromosomal diseases have been evaluated using magnetic resonance imaging. They include patients with trisomy 21, trisomy 18, trisomy 13, 4p-syndrome, 5p-syndrome, and 7p-syndrome. In all these patients karyotype studies were performed demonstrating the chromosomal aberrations. All patients were examined using magnetic resonance imaging to evaluate the head and neck malformations which may be specifically associated with their chromosomal anomaly. We were particularly interested in brain abnormalities and the morphological findings correlated with some pathologic anatomical findings. A review of the literature on neuropathological data is reported and compared with the in vivo anatomical results obtained using this highly anatomical non-ionising and non-invasive investigative procedure. Particular interest is paid to trisomy 21 in which all recognizable stereotyped morphological skull and brain malformations are depicted with magnetic resonance and some other malformations demonstrated such as the excessive forward bending and ascension of the brainstem which correlated well with a simian cephalic organization.