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The distribution of a dopamine D2 receptor mRNA in rat brain.

Based on the recently reported sequence of a dopamine D2 receptor cloned from rat brain, we prepared a series of cDNA probes to determine the distribution of mRNA encoding this receptor. Within the forebrain, D2 receptor mRNA is abundant in the caudate-putamen, accumbens nucleus and olfactory tubercle. Moderate to low levels of mRNA are observed in the medial habenular nucleus, diagonal band, lateral septal nucleus, claustrum, dorsal endopiriform nucleus, and entorhinal cortex. In the mesencephalon, D2 receptor mRNA is abundant within the substantia nigra, pars compacta, and the ventral tegmental area. Comparison of the distribution of the mRNA and ligand binding indicates that both presynaptic and postsynaptic D2 receptors of the nigrostriatal, mesolimbic and mesocortical pathways are derived from the same mRNA.

Animals↗

[Constitutional peculiarities of the bioelectric activity of the brain].

Based on the data obtained in exploring the processes of background bioelectric activity of the brain by means of Karhunen-Lóeve decomposition, the authors have revealed constitutional peculiarities of EEG characterizing the systemic mechanisms of hereditary disposition either to longevity or to cerebral vascular pathology.

Aged↗

[Diagnosis of sarcoidosis of the brain].

Based on 15 years' their own experience and clinical observations of 65 patients with sarcoidosis of the brain, the authors have formulated diagnostic algorithms and a battery of studies that can suspect this disease. Since the clinical manifestations of sarcoidosis of the brain are non-specific, particularly at the early stages of its development, the condition of its recognition is the application of all required high-informative diagnostic neuroimaging techniques that are available to a neurological clinic. Nevertheless, sarcoidosis cannot be timely and correctly recognized in all cases. Diagnostic errors in its recognition are caused by the fact that X-ray computed tomography and/or magnetic resonance imaging is untimely made, tomographic changes are erroneously interpreted, and the studies are conducted improperly.

Brain Diseases↗

Localization of tissue inhibitor of matrix metalloproteinases in Alzheimer's disease and normal brain.

Based upon the hypothesis that metalloproteinases and their inhibitors might be involved in the pathogenesis of Alzheimer's disease, we studied brain samples of eight cases of Alzheimer's disease, six other pathological entities and three elderly controls for tissue inhibitor of metalloproteinase (TIMP) immunoreactivity. Specificity was supported by a loss of immunoreactivity following antigen preabsorption of antisera. Areas studied included ependyma, choroid plexus, frontoparietal, hippocampal and cerebellar cortex, n. basalis of Meynert, basal ganglia, midbrain, pons, and medulla. TIMP positivity was localized to neuritic senile plaques, neurofibrillary tangles and Purkinje cells. The pattern of TIMP plaque staining was similar to that observed with anti tau and SP18 antibodies. It differed from that observed with anti SP40, HAM 56 and GFAP antibodies. The selective localization of TIMP to the neuritic lesions of Alzheimer's disease in a codistribution with the amyloid precursor protein and abnormally phosphorylated and truncated tau supports a possible role for metalloproteinases and their inhibitors in the evolution of these lesions.

Aged↗

Rapid prototyping of an EEG-based brain-computer interface (BCI).

The electroencephalogram (EEG) is modified by motor imagery and can be used by patients with severe motor impairments (e.g., late stage of amyotrophic lateral sclerosis) to communicate with their environment. Such a direct connection between the brain and the computer is known as an EEG-based brain-computer interface (BCI). This paper describes a new type of BCI system that uses rapid prototyping to enable a fast transition of various types of parameter estimation and classification algorithms to real-time implementation and testing. Rapid prototyping is possible by using Matlab, Simulink, and the Real-Time Workshop. It is shown how to automate real-time experiments and perform the interplay between on-line experiments and offline analysis. The system is able to process multiple EEG channels on-line and operates under Windows 95 in real-time on a standard PC without an additional digital signal processor (DSP) board. The BCI can be controlled over the Internet, LAN or modem. This BCI was tested on 3 subjects whose task it was to imagine either left or right hand movement. A classification accuracy between 70% and 95% could be achieved with two EEG channels after some sessions with feedback using an adaptive autoregressive (AAR) model and linear discriminant analysis (LDA).

Adolescent↗

Experimental and theoretical analysis of oxygen transport in fetal brain.

Based on the results obtained in this study and the results of others it seems safe to conclude the following: 1) Fetal brain PO2 values are considerably lower than those found in adult brain. 2) Administration of 100% oxygen to the mother can (but not always) significantly raise the PO2 at a specific point in the fetal cortex. 3) The response of fetal brain PO2 to changes in maternal arterial PO2 is delayed by a finite quantity of time of the order of magnitude of 38 seconds. 4) The time required for the fetal brain PO2 to reach a minimum following a decrease in the PO2 of maternal arterial blood coincides closely with the time required for the maternal arterial PO2 to reach its minimum plus the pure transport delay time (38 seconds). 5) The fetus has available a control mechanism which acts to compensate for periods of reduced PO2 in the microenvironment of the fetal cortex.

Animals↗

Some problems for representations of brain organization based on activation in functional imaging.

Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of brain damage. However, the enthusiastic onslaught of brain images, frequently presented as veridical representations of mental function, has sometimes overwhelmed some basic facts about brain organization repeatedly observed over more than a century. In particular, the lateralization of speech and language to the left cerebral hemisphere in over 90% of the right-handed population does not appear to have been taken as a serious constraint in the interpretation of imaging results in studies of these functions. This paper reviews a number of areas in which standard activation assumptions yield results that are at odds with clinical experience. The activation approach will be contrasted with a performance-based analysis of functional image data, which, at least in the case of speech production, yields results in better agreement with lesion data. Functional imaging represents enormous opportunities for understanding brain-behavior relationships, but at the present level of understanding of what is being represented in such images, it is premature to adhere to a single approach based on the strong but questionable assumptions inherent in most activation studies.

Animals↗

Lack of mitochondrial nitric oxide production in the mouse brain.

Based on our initial finding that the nitric oxide (NO) sensitive fluorochrome diaminofluorescein (DAF) was localized to mitochondria in cultured primary neurons, we investigated whether brain mitochondria produce NO through a mitochondrial NO synthase (mtNOS) enzyme. Isolated brain mitochondria were loaded with DAF and subjected to flow cytometry analysis. Neither the application of NOS inhibitors nor the genetic disruption of either NOS gene diminished the DAF-fluorescence. However, peroxynitrite scavengers reduced the mitochondrial DAF fluorescence, indicating that the DAF signal is not specific to NO. Chemiluminescence detection in the head space gas and a Clark-type NO-sensitive electrode in the solution failed to detect NO release in brain mitochondria. NOS activity in mitochondria was only 1% of the whole brain NOS activity level, which may be attributed to extramitochondrial contamination. Extensive immunoblotting and immunoprecipitation experiments failed to show the presence of endothelial, neuronal, or inducible NOS in mouse brain mitochondria using a variety of primary antibodies. Arginine, calmodulin or 2,5-ADP affinity purification protocols successfully concentrated eNOS and nNOS from full brain tissue but failed to show any signal in mitochondria. We conclude that mouse brain mitochondria do not contain NOS isoforms, nor do they produce NO through a NOS-dependent mechanism.

Animals↗

The neurosecretory system of the adult Melanogryllus desertus Pall. (Orthoptera, Gryllidae). I. Ultrastructural study of the median neurosecretory cells in the brain.

Based on the nature of their granules, eight prinicipal types of neurons, six of which are thought to be neurosecretory, are recognized in the median neurosecretory cell group of the brain of Melanogryllus desertus. Most of the neurosecretory cells contain granules with diameters of 200-300 nm. In a few the granules are smaller with diameters varying from 60-100 nm. Most of the cells have well developed Golgi areas and dense bodies of different sizes. Dense bodies are closely associated the neurosecretory granules. Accumulations of electron-dense granular material occur in expanded cisterns of endoplasmic reticulum, particularly in type-I cells.

Animals↗

An argyrophil-III method for the selective demonstration of mitochondria in aldehyde-fixed rat brain.

Based on recent achievements in physicochemical aspects of histological silver staining, a selective and reliable method was elaborated for the demonstration of mitochondria in frozen sections of aldehyde-fixed rat brain. Areas of similar architecture were stained with comparable intensity both within one section or in serial sections. The distribution patterns of mitochondria can be examined at low magnification or even with the unaided eye. At high magnifications, rounded and elongated profiles with the size and shape of mitochondria clearly stand out against a pale background. Electron microscopy revealed a high degree of selectivity and completeness of the mitochondrial staining.

Aldehydes↗

Design of an EEG-based brain-computer interface (BCI) from standard components running in real-time under Windows.

An EEG-based brain-computer interface (BCI) is a direct connection between the human brain and the computer. Such a communication system is needed by patients with severe motor impairments (e.g. late stage of Amyotrophic Lateral Sclerosis) and has to operate in real-time. This paper describes the selection of the appropriate components to construct such a BCI and focuses also on the selection of a suitable programming language and operating system. The multichannel system runs under Windows 95, equipped with a real-time Kernel expansion to obtain reasonable real-time operations on a standard PC. Matlab controls the data acquisition and the presentation of the experimental paradigm, while Simulink is used to calculate the recursive least square (RLS) algorithm that describes the current state of the EEG in real-time. First results of the new low-cost BCI show that the accuracy of differentiating imagination of left and right hand movement is around 95%.

Amyotrophic Lateral Sclerosis↗

A study of childhood brain tumors based on surgical biopsies from ten North American institutions: sample description. Childhood Brain Tumor Consortium.

The Childhood Brain Tumor Consortium has collected an extensive amount of neuropathologic and clinical information under rigorously controlled conditions about 3,291 children with brain tumors. In this overview of the entire sample, five observations are prominent: 1) many tumors involve more anatomic sites at the time of the first surgical exploration than previously recognized; 2) one-third of infratentorial tumors involve both the brainstem and the cerebellum; 3) the spinal compartment is involved primarily, or in combination with the posterior fossa, in 11% of childhood brain tumors; 4) 43.2% of childhood brain tumors are limited to the posterior fossa; 5) only a few World Health Organization diagnoses account for most brain tumors in children, and 6) there is a male predominance over all ages for infratentorial tumors. Subsequent reports will describe observer variability of participating neuropathologists, correlates of clinical and histologic information, the search for homogeneous subtypes of tumors, and prognostic factors.

Adolescent↗

Development of an in vitro blood-brain barrier model based on immortalized porcine brain microvascular endothelial cells.

Immortalized porcine brain microvessel endothelial cells (PBMEC/C1-2) were used to develop a model for measurement of blood-brain barrier permeation of central nervous system active drugs. Previous studies showed that a system using C6 astrocyte glioma conditioned medium leads to cell layers with transendothelial electrical resistance values up to 300 Omega cm(2) and a permeability coefficient P(e) of 3.24 +/- 0.14 x 10(-4) cm/min for U-[(14)C]sucrose, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro. However, commercially available inserts for the Transwell system were not permeable for highly lipophilic compounds, such as diazepam. Systematic studies with different insert showed, that inserts with a pore width of 1 microm proved to be optimal for permeation studies of lipophilic compounds. Permeability studies with a set of three benzodiazepines further supported this finding.

Animals↗

Influence of iron-saturation of plasma transferrin in iron distribution in the brain.

Based on the evidence that iron distribution in the peripheral tissues is changed by iron-saturation of plasma transferrin, the influence of iron-saturation of plasma transferrin in iron delivery to the brain was examined. Mouse plasma was pre-incubated with ferric chloride in citrate buffer to saturate transferrin and then incubated with (59)FeCl(3). Peak retention time of (59)Fe was transferred from the retention time of transferrin to that of mercaptalbumin, suggesting that iron may bind to albumin in the plasma in the case of iron-saturation of transferrin. When mice were intravenously injected with ferric chloride in citrate buffer 10 min before intravenous injection of (59)FeCl(3), 59Fe concentration in the plasma was remarkably low. (59)Fe concentration in the liver of iron-loaded mice was four times higher than in control, while 59Fe concentration in the brain of iron-loaded mice was approximately 40% of that of control mice. Twenty-four hours after intravenous injection of (59)FeCl(3), brain autoradiograms also showed that (59)Fe concentrations in the brain of iron-loaded mice were approximately 40-50% of those of control mice in all brain regions tested except the choroid plexus, in which (59)Fe concentration was equal. These results suggest that the fraction of non-transferrin-bound iron is engulfed by the liver, resulting in the reduction of iron available for iron delivery to the brain in iron-loaded mice. Transferrin-bound iron may be responsible for the fraction of iron in circulation that enters the brain.

Animals↗

Differential expression of the 61 kDa and 63 kDa calmodulin-dependent phosphodiesterases in the mouse brain.

Based on their relative abundance and regulation by Ca2+ and by phosphorylation in vitro, it is thought that the Ca2+/calmodulin-dependent phosphodiesterases (CaM-PDEs) are important modulators of cyclic nucleotide function in the brain. Two of the most abundant CaM-PDEs in the brain are the 61 kDa and 63 kDa isozymes. In this study, the regional and cellular expression of mRNA encoding these two different isoforms in mouse brain has been determined by in situ hybridization. The 63 kDa CaM-PDE mRNA has a wide-spread but uneven distribution. Very strong hybridization signals are present in the caudate-putamen, nucleus accumbens, olfactory tubercle, and dentate gyrus of the hippocampus. Somewhat lesser amounts of 63 kDa CaM-PDE mRNA are present in the olfactory bulb and piriform cortex. Weaker but still easily discernible hybridization signals are seen in several layers of the cerebral cortex, CA1 and CA3 regions of the hippocampus, amygdaloid nuclear complex, thalamus, hypothalamus, midbrain, brainstem, cerebellum, and spinal cord. A weak hybridization signal was detected in the globus pallidus of the basal ganglia. In general, the distribution of the 63 kDa CaM-PDE is very similar to that of dopamine receptors, suggesting that it may modulate dopamine function. In contrast, the 61 kDa CaM-PDE mRNA has a more limited and much different distribution, with the highest level of expression in the cerebral cortex and in the pyramidal cells of the hippocampus. A moderate hybridization signal was detected in the medial habenula and amygdaloid nuclear complex. In addition, small subsets of neurons in several other regions showed specific hybridization. Both PDE mRNAs appear to be localized exclusively in neuronal cell bodies. Their distinct distribution suggests important but different physiological roles for these two isozymes in the regional regulation of cyclic nucleotides in the CNS. Since these two isozymes are differentially phosphorylated by cAMP-dependent and Ca2+/CaM-dependent protein kinases, the differential expression also provides a potential mechanism by which these PDEs can differentially regulate cAMP and cGMP in different brain areas. The high expression levels in specific subsets of neurons also suggest that agents increasing Ca2+ in these neurons will increase the rate of cyclic nucleotide degradation.

Animals↗

Dynamic process of information transmission complexity in human brains.

Based on a complexity analysis of mutual information transmission of EEG developed by us [Xu J, Liu Z, Liu R, Yang Q (1997) Physica D 106: 363-374], dynamic processes of the complexity of mutual information transmission in human brains were studied. To diminish possible problems due to coarse graining preprocessing, some new measures of complexity were used. The results show that, just before and after generalized seizures, the complexities of almost all information transmission between different brain areas drop significantly; there is also a temporary decrease of complexity when subjects shift their attention. The above facts suggest that there is a transient decrease of information transmission complexity when brain state changes occur suddenly. Mental arithmetic tasks activate the left temporal lobe to exchange more information with other brain areas. The results hint that the methods used here might be an approach to observe quick processes in the living brain.

Adult↗

Olfactory asymmetry in the rat brain.

Based on cytoarchitecture, myeloarchitecture, and physiological observations in the literature, two concentric strata are identified in the olfactory bulb of the albino rat. Stimulated by a report of physiologic asymmetry between the left and right bulb of the rodent brain, we parcelled the inner and outer strata of the olfactory bulbs of 16 albino rats and measured the volume of these olfactory subdivisions. The volume of the entire olfactory bulb was found to be significantly greater in the right hemisphere. This volume asymmetry was the result of a significantly larger right outer stratum. No significant asymmetry was demonstrated for the inner stratum. These findings are discussed in the light of some physiologic and anatomic properties of the olfactory bulb.

Animals↗

Regional distribution of guanine nucleotide-sensitive and guanine nucleotide-insensitive vasoactive intestinal peptide receptors in rat brain.

Based on the ability of guanine nucleotides to inhibit the binding of vasoactive intestinal peptide to its receptors, a guanosine 5'-triphosphate analog, guanylyl-imidodiphosphate, was used to differentiate two subtypes (or different functional states of a single subtype) of vasoactive intestinal peptide receptor in brain with in vitro autoradiography. In most brain regions, guanylyl-imidodiphosphate reduced vasoactive intestinal peptide binding between 40 and 60%. However, in the supraoptic nucleus, locus coeruleus, interpeduncular nucleus, facial nucleus, olfactory tubercle and periventricular hypothalamic nucleus, 80% or more of vasoactive intestinal peptide binding was inhibited. In other brain regions, including the medial geniculate, olfactory bulbs, and ventral thalamic nuclei, guanylyl-imidodiphosphate had little effect on vasoactive intestinal peptide binding. In liver, lung and intestine it also partly inhibited vasoactive intestinal peptide binding. Electrophoretic analysis of vasoactive intestinal peptide, covalently cross-linked to its receptors in brain membranes, revealed a pair of bands between 44,000 and 52,000 mol. wt, a component at 64,000 mol. wt and another at 92,000 mol. wt. All were displaceable with vasoactive intestinal peptide but guanylyl-imidodiphosphate displaced only the 64,000 mol. wt band suggesting that the GTP-sensitive vasoactive intestinal peptide receptor seen in brain sections has a molecular weight of about 61,000. The differential sensitivity to guanylyl-imidodiphosphate suggests the existence of at least two vasoactive intestinal peptide receptor subtypes in brain, with distinct regional distribution, and may reflect differential coupling to second messenger systems.

Animals↗