Altered relationships between rCBF in different brain regions of never-treated schizophrenics

AIM: of this study was to investigate the relations between regional cerebral blood flow (rCBF) of different brain regions in acute schizophrenia and following neuroleptic treatment. METHODS: Twenty-two never-treated, acute schizophrenic patients were examined with HMPAO brain SPECT and assessed psychopathologically, and reexamined following neuroleptic treatment (over 96.8 days) and psychopathological remission, rCBF was determined by region/cerebellar count quotients obtained from 98 irregular regions of interest (ROIs), summed up to 11 ROIs on each hemisphere. In acute schizophrenics, interregional rCBF correlations of each ROI to every other ROI were compared to the interregional correlations following neuroleptic treatment and to those of controls. RESULTS: All significant correlations of rCBF ratios of different brain regions were exclusively positive in controls and patients. In controls, all ROIs of one hemisphere except the mesial temporal ROI correlated significantly to its contralateral ROI. Each hemisphere showed significant frontal-temporal correlations, as well as cortical-subcortical and some cortico-limbic. In contrast, in acute schizophrenics nearly every ROI correlated significantly with every other ROI, without a grouping or relation of the rCBF of certain ROIs as in controls. After neuroleptic treatment and clinical improvement, this diffuse pattern of correlations remained. CONCLUSIONS: These results indicate differences in the neuronal interplay between regions in schizophrenic and healthy subjects. In never-treated schizophrenics, diffuse interregional rCBF correlations can be seen as a sign of change and dysfunction of the systems regulating specificity and diversity of the neuronal functions. Neuroleptic therapy and psychopathologic remission showed no normalizing effect on interregional correlations.     

Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics: evidence for glutamate hypothesis

Strychnine-insensitive glycine binding sites, an absolute requirement of the responses mediated by N-methyl-D-aspartate (NMDA) receptors, were measured in the postmortem brains of 13 chronic schizophrenics and 10 controls, using a radiolabeled receptor assay. Specific [3H]glycine binding was significantly increased in six of the 16 areas of the cerebral cortex that were investigated. Scatchard analysis performed in these areas showed a significant increase in the maximum number of binding sites, with no change in the affinity of binding. Multiple regression analysis confirmed that the increase was not due to age at death or interval from death to freezing. The increase was also observed in the off-drug cases of schizophrenics who had not taken antipsychotics for more than 40 days before death. These results suggest that the increases in NMDA-associated glycine binding sites, possibly ascribed to the postsynaptic compensation for impaired glutamatergic neurotransmission, might be implicated in the pathophysiology of schizophrenia.     

Activation PET scanning in pretreatment evaluation of patients with cerebral tumours or vascular lesions in or close to the sensorimotor cortex

Calmodulin is a ubiquitous transducer of calcium signals in eukaryotes. In diploid plant species, several isoforms of calmodulin have been described. Here, we report on the isolation and characterization of calmodulin cDNAs corresponding to 10 genes from hexaploid (bread) wheat (Triticum aestivum). These genes encode three distinct calmodulin isoforms; one isoform is novel in that it lacks a conserved calcium binding site. Based on their nucleotide sequences, the 10 cDNAs were classified into four subfamilies. Using subfamily-specific DNA probes, calmodulin genes were identified and the chromosomal location of each subfamily was determined by Southern analysis of selected aneuploid lines. The data suggest that hexaploid wheat possesses at least 13 calmodulin-related genes. Subfamilies 1 and 2 were both localized to the short arms of homoeologous-group 3 chromosomes; subfamily 2 is located on all three homoeologous short arms (3AS, 3BS and 3DS), whereas subfamily 1 is located only on 3AS and 3BS but not on 3DS. Further analysis revealed that Aegilops tauschii, the presumed diploid donor of the D-genome of hexaploid wheat, lacks a subfamily-1 calmodulin gene homologue, whereas diploid species related to the progenitors of the A and B genomes do contain such genes. Subfamily 3 was localized to the short arm of homoeologous chromosomes 2A, 2B and 2D, and subfamily 4 was mapped to the proximal regions of 4AS, 4BL and 4DL. These findings suggest that the calmodulin genes within each subfamily in hexaploid wheat represent homoeoallelic loci. Furthermore, they also suggest that calmodulin genes diversified into subfamilies before speciation of Triticum and Aegilops diploid species.     

Impaired autoregulation in an experimental model of chronic cerebral hypoperfusion in rats

BACKGROUND AND PURPOSE: To verify the hypothesis that impaired autoregulation may contribute to cerebral swelling or hemorrhage after a sudden recovery of perfusion pressure, we studied the chronic effects of cerebral hypoperfusion on the autoregulatory responses of the pial arterioles in situ. METHODS: Eight to 12 weeks after a carotid-jugular fistula was created in rats, experiments were performed under alpha-chloralose and urethane anesthesia. Regional cerebral blood flow (rCBF) was determined by the hydrogen clearance method, and carotid pressure was measured. Using a closed cranial window, we determined the autoregulatory responses of the arterioles (30 to 50 microns) to both hypertension induced by norepinephrine and sudden fistula closure at various mean arterial pressures (MAPs). RESULTS: rCBF on the fistula side was reduced by 27%. Carotid pressure was significantly lower than normal but was immediately increased by fistula closure. The pial arterioles showed marked elongation and enlargement. During induced hypertension, the arterioles in the fistula group started to dilate at an MAP lower than that of the control group (130 versus 180 mm Hg, respectively). The arterioles constricted when the fistula was occluded at normal MAP. However, when the fistula was occluded at an MAP higher than 130 mm Hg, the vessels dilated. CONCLUSIONS: It was demonstrated that (1) chronic hypoperfusion induced impairment of the upper limit of autoregulation and (2) sudden fistula closure under hypertensive conditions caused vasodilation of the arterioles. These findings suggest that rapid restoration of perfusion pressure is possibly followed by a pressure breakthrough phenomenon in a chronically hypoperfused cerebrovasculature.     

Correlation between whole blood cholinesterase activity and cerebral cortex cholinesterase activity in rats treated with parathion

Organophosphate and carbamate insecticides are inhibitors of cholinesterases (ChE). The depression of blood ChE activity is frequently used as indicative of exposure to these chemicals. However, it is not known whether the inhibition of blood ChE activity reflects the inhibition of ChE in target tissues (e.g. brain and muscle). In this study we investigated the possibility of using whole blood ChE activity to predict frontal cerebral cortex ChE activity in rats treated with parathion. Twenty four hours after the intraperitoneal administration of several doses of parathion, the activity of ChE in whole blood and the activity of ChE in frontal cerebral cortex were determined in each animal. A high correlation between the two parameters was found (r = 0.96, p < 0.05) and the model of linear regression fitted to the data accounted for 93% of its variability. Thus, these results seem to indicate that 24 hours after the treatment with parathion the effects induced on whole blood ChE activity may be used to predict the effects caused on frontal cerebral cortex ChE activity.     

A light and electron microscopic study of HLA-DR positive cells in the human cerebral cortex and subcortical white matter

Specimens of histologically normal human cerebral cortex and subcortical white matter were obtained during neurosurgical operations and studied by electron microscopy and immunocytochemistry using an antibody against HLA-DR. Greater numbers of labelled cells were present in the white matter than in the overlying cortex. The labelled cells consisted of ramified microglia and perivascular cells. Microglia were often found just outside the walls of small blood vessels, but perivascular cells were actually enclosed by two leaflets of basement membrane in the walls of capillaries, arterioles and venules up to 100 microns in luminal diameter. Labelled microglial processes were often seen enclosing neuronal processes in the cortex and myelinated and unmyelinated axons in the white matter. The enclosed processes appeared healthy, and without features of degenerating neurons. These observations are consistent with a previous suggestion that microglia continually modify the processes of central nervous system neurons by a process of phagocytosis. An intact blood-brain barrier is likely to be of great importance in preventing antigen presentation of the processed neuronal, and perhaps even oligodendrocytic, antigenic peptide fragments to circulating lymphocytes.     

Regional cerebral hypoperfusion reduces the effect of rectal midazolam in children with Moyamoya disease

To investigate the effect of regional cerebral blood flow on the effect of midazolam, we evaluated 99mTc-hexamethylpropylene-amine-oxime-single photon emission computed tomography (SPECT) in 37 cases of childhood moyamoya disease. They were divided into two groups according to the findings of SPECT; one group showed hypoperfusion in the bifrontal regions (n = 20), and the other did not (n = 17). Both groups received 1 mg.kg-1 of midazolam transrectally 30 min before the anesthesia induction and level of sedation was measured with six point scales. Significantly lower level of sedation score was recognized in the group that showed hypoperfusion in bifrontal regions (P < 0.05). Our finding may suggest that regional cerebral hypoperfusion may modify the sedative effect of midazolam in children with moyamoya disease.     

Neurono-glial changes in the cerebral cortex of animals exposed to white noise

The rat acoustic cortex has been studied at light optic and ultrastructural levels under the white noise stimulation. After the noise stimulation for 7 days, micropunctate hemorrhages, proliferation and hypertrophy in cells of microglia and astrocytic glia are noted. After the noise stimulation for 21 days, the neuroglial reaction becomes less pronounced, there are no hemorrhages, a great amount of neurons with peripheral and total chromatolysis appear. In other neurons, as well as in all types of neuroglia the number of primary lysosomes increases, their structure changes. In lysosomes lipofuscin and lipid drops are accumulating, many of lysosomes turning into multivesicular bodies. The destructive changes observed in the neurons and neuroglia underlie prolonged disturbances in the higher neural activity after the noise stimulation is stopped.     

Arousal response to electrical stimulation of the cerebral cortex in cats.

Questions the belief that the arousal response produced by stimulation at various sites in the cortex is due to direct stimulation of the cortical component of a central arousal system. 3 observations of 9 female and 2 male cats were not consistent with this interpretation. Fractionation of the arousal response, subtotal parts of the reaction being produced by varying the intensity of cortical stimulation, occurred only when the S was in the resting state, and the arousal response habituated during repeated cortical stimulation. These observations on the arousal response to cortical stimulation were duplicated closely by the arousal response to an auditory stimulus. In agreement with a 1967 study by H. Ursin, K. Wester, and R. Ursin, it is suggested that the arousal response to stimulation of the cortex is a reflex to a sensory experience created by cortical stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypervascularization of the cerebral cortex in lead-induced encephalopathy

Pregnant rats were fed a diet containing 1.8% lead acetate for 8 days before delivery until the young were 3 month old. The density of the cerebral cortex capillaries of the infant rats and their convolution rate were studied morphometrically and noted to increase significantly according to the duration of lead treatment, as demonstrated by two-way analysis of variance. On the other hand, the thickness of the cortex reduced progressively. The increase of both capillary density and convolution rate is supposed to be related with this involution of cortex. This provides a quantitative insight of the previously described 'capillary activation' phenomenon, caused by lead encephalopathy and reveals it as a significant sequel of saturnine action.     

The cerebral control of the somatosensory and auditory afferent projections to the cerebral cortex in man and animals

The main purpose of the present paper was consisted in studying of topology (spreading) of the somatosensory and auditory projections in cortex of both brain hemispheres in humans under different functional states conditions: during quiet walking state and during realization of the meditative programme. At the same time for the purpose of verification these steering mechanisms a number of experiments were realized in animals with neurosurgical cutting of brainstem ascending projections, which control the transfer of somatosensory and auditory sensibility. Experimental study was realized with two groups of subjects--8 subjects (age from 25 to 35 years old) and 25 (age from 25 to 40 years old) subjects practicing technique of Transcendental Meditation (TM). In addition to the mentioned above group some groups of animals were used in the experiments. Among them there were used the groups of monkeys (8 macaque rhesus and macaque nemestrina) and cats (10 animals) in conditions of acute experiment, under tiopenthal anesthesia. Two experimental methods were used in the study: electrophysiological for subjects and neurosurgical, additionally for animals. For evaluation of the brain reactivity in subjects registration of the somatosensory, to median nerve stimulation, and auditory, to bilateral application of auditory clicks, evoked potentials (EPs) in the symmetrical cortical structures of the brain was used. Registration of the somatosensory and auditory evoked potentials in animals was realized not only from the cortex, but from the brainstem somatosensory and auditory structures. SSEP in subjects-meditators were registered before and during meditation programme. In animals SSEP and AEP registration on the corresponding stimuli realized before and after neurosurgical operation--section of the midbrain tegmentum. Specific alterations of the early (up to 80 ms) and late components SSEP and AEP complexes in forms of topology spreading and diminution of registration areas of these components were obtained during the meditation. Origins of these functional reorganization are discussed from the positions of internal 'feed-back' inhibition.     

Verbal paired-associates learning in chronic schizophrenics as a function of positive and negative evaluation.

Seventy-two chronic schizophrenics (36 regressed and 36 partially remitted) and 36 normals were given paired associates of 2 levels of association strength and 2 levels of intralist response competition to learn under positive, negative, and nonevaluation conditions. Regressed schizophrenics showed maximum decrement on low-association word pairs following positive evaluation. This was especially true for those Ss with low self-esteem. These findings suggest that heightened arousal resulting from dissonance between a negative self-image and positive evaluation of performance can lead to behavioral decrement in a difficult task requiring novel associations, such decrement being congruent with the Hull-Spence behavior theory and the Yerkes-Dodson hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy

BACKGROUND: Positron emission tomographic and postmortem studies comparing schizophrenic patients with healthy control subjects have found medial prefrontal cortical and anterior cingulate abnormalities that suggest dysfunction in glutamatergic neurons. The glutamate used for nerve signal transduction is predominantly derived from glutamine. After signal transduction, glutamate released into the synapse is converted to glutamine in glial cells, transported back to the presynaptic neuron, and reconverted to glutamate for reuse. In this study, levels of glutamate and glutamine were examined by means of in vivo proton (1H) magnetic resonance spectroscopy. METHODS: Localized in vivo 1H spectra were acquired from a 4.5-cm3 volume in the left medial prefrontal cortex encompassing portions of Brodmann areas 24, 32, and 9 in 10 never-treated schizophrenic subjects and 10 healthy controls of comparable age, sex, handedness, education, and parental education. From each spectrum, metabolite levels were estimated for glutamate and glutamine, as well as 10 other metabolites and 3 macromolecules, by means of a noninteractive computer program that combined modeled in vitro spectra of every metabolite to reconstruct each in vivo spectrum. RESULTS: A significant increase in glutamine level was found in the medial prefrontal cortex of the schizophrenic patients compared with controls. N-acetylaspartate and other measured metabolites and macromolecules were not significantly changed in schizophrenics. CONCLUSION: Increased glutamine levels in the medial prefrontal region most likely reflect decreased glutamatergic activity in this region in never-treated schizophrenic patients compared with healthy controls.     

Mathematical model of oxygen transport in the cerebral cortex

To estimate the magnitude of hyperemia necessary to support oxidative metabolism in the cerebral cortex during functional activation, a mathematical model of O2 transport from capillary to tissue was developed. Radial and axial gradients of O2 pressure in tissue surrounding a single capillary were calculated at normal and increased cerebral metabolic rates for O2. Cone-shaped tissue geometry and nonlinear oxyhemoglobin dissociation were assumed. Local O2 consumption was assumed to be supported with local tissue pO2 greater than 1 mmHg. The distribution of tissue pO2 was also calculated during moderate hypoxemia (paO2=42 mmHg), using experimental values of red blood cell velocity measured in individual capillaries of the rat cerebral cortex using intravital video-microscopy. The model predicted that moderate increases (相似文献   

Salient features of synaptic organisation in the cerebral cortex

The neuronal and synaptic organisation of the cerebral cortex appears exceedingly complex, and the definition of a basic cortical circuit in terms of defined classes of cells and connections is necessary to facilitate progress of its analysis. During the last two decades quantitative studies of the synaptic connectivity of identified cortical neurones and their molecular dissection revealed a number of general rules that apply to all areas of cortex. In this review, first the precise location of postsynaptic GABA and glutamate receptors is examined at cortical synapses, in order to define the site of synaptic interactions. It is argued that, due to the exclusion of G protein-coupled receptors from the postsynaptic density, the presence of extrasynaptic receptors and the molecular compartmentalisation of the postsynaptic membrane, the synapse should include membrane areas beyond the membrane specialisation. Subsequently, the following organisational principles are examined: 1. The cerebral cortex consists of: (i) a large population of principal neurones reciprocally connected to the thalamus and to each other via axon collaterals releasing excitatory amino acids, and, (ii) a smaller population of mainly local circuit GABAergic neurones. 2. Differential reciprocal connections are also formed amongst GABAergic neurones. 3. All extrinsic and intracortical glutamatergic pathways terminate on both the principal and the GABAergic neurones, differentially weighted according to the pathway. 4. Synapses of multiple sets of glutamatergic and GABAergic afferents subdivide the surface of cortical neurones and are often co-aligned on the dendritic domain. 5. A unique feature of the cortex is the GABAergic axo-axonic cell, influencing principal cells through GABAA receptors at synapses located exclusively on the axon initial segment. The analysis of these salient features of connectivity has revealed a remarkably selective array of connections, yet a highly adaptable design of the basic circuit emerges when comparisons are made between cortical areas or layers. The basic circuit is most obvious in the hippocampus where a relatively homogeneous set of spatially aligned principal cells allows an easy visualization of the organisational rules. Those principles which have been examined in the isocortex proved to be identical or very similar. In the isocortex, the basic circuit, scaled to specific requirements, is repeated in each layer. As multiple sets of output neurones evolved, requiring subtly different needs for their inputs, the basic circuit may be superimposed several times in the same layer. Tangential intralaminar connections in both the hippocampus and isocortex also connect output neurones with similar properties, as best seen in the patchy connections in the isocortex. The additional radial superposition of several laminae of distinct sets of output neurones, each representing and supported by its basic circuit, requires a co-ordination of their activity that is mediated by highly selective interlaminar connections, involving both the GABAergic and the excitatory amino acid releasing neurones. The remarkable specificity in the geometry of cells and the selectivity in placement of neurotransmitter receptors and synapses on their surface, strongly suggest a predominant role for time in the coding of information, but this does not exclude an important role also for the rate of action potential discharge in cortical representation of information.