Microsphere embolism-induced changes in presynaptic function of the cerebral cortex in rats

The present study was undertaken to elucidate pathophysiological changes in the cortical presynaptic function, K(+)-stimulated calcium influx, noradrenaline release and noradrenaline uptake, on the 1st and 3rd days after microsphere embolism in rats. Voltage-dependent calcium channels were characterized pharmacologically using three types of calcium channel blockers, L-type (nifedipine and diltiazem), N-type (omega-conotoxin GVIA), and P-type channel (omega-agatoxin IVA) blockers. K(+)-stimulated calcium influx of the normal rat synaptosome was inhibited by 100 nM omega-agatoxin IVA, but not by 10 microM nifedipine, 10 microM diltiazem and 100 nM omega-conotoxin GVIA. Calcium influx of the cortical nerve terminals of the right hemisphere was decreased on the 1st and 3rd days after the embolism. Noradrenaline release and uptake were also decreased on the 1st and 3rd days after the embolism. However, the percent release of noradrenaline was not altered. The results suggest that P-type channels are predominant in the cerebrocortical nerve terminals in rats and that calcium influx, noradrenaline release and uptake in the cerebrocortical nerve terminals are decreased by microsphere embolism. The decrease in noradrenaline release may be mainly due to a reduction in the activity of noradrenaline uptake in cerebrocortical nerve terminals of the microsphere-embolized rat.     

Bilateral neuropathologic changes in a child with hemimegalencephaly

Evaluation of a 7-month-old girl with developmental delay and intractable seizures revealed hemispheric asymmetry and an enlarged right cerebral hemisphere. Because of a history of seizures refractory to medical therapy, she was admitted for right hemispherectomy, but died of complications of surgery. Postmortem brain examination revealed asymmetric enlargement of the right cerebral hemisphere but no gross abnormalities in the left hemisphere. Microscopic examination demonstrated bilateral neuropathologic changes consistent with severe cortical dysplasia in the right cerebral hemisphere and mild cortical dysplasia in the left. Although white matter abnormalities in the unaffected hemisphere have been reported in hemimegalencephaly, bilateral cortical abnormalities, not reported previously in patients with hemimegalencephaly, may account for the varied clinical outcome with medical therapy or after hemispherectomy.     

Microsphere embolism-induced changes in noradrenaline release in the cerebral cortex in rats

A human cell line LMS6-93 has been established from a leiomyosarcoma (LMS). Characteristics for ultrastructure, growth characteristics, cell cycle distribution, karyotype, protein expression detected by immunohistochemistry (IHC), p53 mutational status and liposomal transfection behaviour were studied and determined. The primary tumor was clearly positive for á-smooth muscle type actin and desmin in moderately differentiated areas and indicated a loss of myogenic differentiation in other regions and therefore was classified as a poorly differentiated LMS. The cell line LMS6-93 contains mainly polymorphic spindle shaped or polygonal tumor cells which possess the characteristics of primitive mesenchymal cells, based on their morphology and positive reaction with an antibody to vimentin. IHC staining for S100, synaptophysin A, NSE, neurofilament proteins and cytokeratins were negative. Cytogenetic analysis revealed in the cell line diploid karyotypes comparatively close to several structural and numerical aberrations for chromosomes 2, 5, 6, 9, 10, 12, 14, 17, 18, 20, 22, and Y. IHC positivity was found for the tumor suppressor protein Rb and the oncogene product MDM2. In a p53 mutational analysis a 1 bp insertional mutation in exon 6 (G insertion in codon 215) was detected and confirmed in the original primary tumor. The other p53 allele appears to be wild-type as indicated in Western hybridization. Using different cationic lipid formulations complexed with a reporter expression vector (GFP) successful transfection into LMS6-93 cells was observed. The highest transfection rates (20-30% GFP expression in the viable cell population) were obtained with lipofectin. These results suggest that LMS6-93 functions as a good in vitro model for transfection studies on an LMS cell line carrying a heterozygous p53-frameshift mutation.     

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.     

Quantitative morphological analysis of subicular terminals in the rat entorhinal cortex

In the present report, we describe a morphological and quantitative analysis of subicular synapses in layer V of the lateral entorhinal cortex (LEA) of the rat. Projections from the dorsal subiculum were labeled anterogradely, and areas in LEA showing high terminal density were randomly selected for ultrathin sectioning. More than 400 terminals in LEA were photographed in the electron microscope, and synapse types and postsynaptic targets were identified and, subsequently, quantified with the unbiased disector method. Most subicular terminals appeared to form asymmetrical synapses. A majority of asymmetrical synapses terminated on spines (67.5%), whereas a smaller fraction of asymmetrical synapses (23.5%) terminated on dendritic shafts. A small fraction of the terminals (7%) had symmetrical features. These symmetrical synapses had an almost equal percentage of spines and dendritic shafts as postsynaptic elements. Labeled synapses on somata or axons were never observed. The findings of this study in conjunction with relevant electrophysiological observations (Jones [1987] Neurosci Left 81:209-214) leads to the conclusion that the subiculo-entorhinal pathway comprises a large excitatory and a smaller inhibitory projection, both making synaptic contacts with presumed principal neurons and interneurons in the entorhinal cortex.     

Quantitative and ultrastructural changes in glia and pericytes in the parietal cortex of the aging rat

Glutathione S-transferases (GSTs) are essential detoxification enzymes for virtually all cells and may additionally aid in parasite survival by counteracting host-induced damage. GSTs from parasitic nematodes have been identified as potential targets for both immuno- and chemotherapy. To more closely characterize a 31-kDa (OvGST1) and a 24.5-kDa (OvGST2) GST from the pathogenic human filarial parasite Onchocerca volvulus, immunolocalization by electron microscopy was performed using two distinct affinity-purified polyclonal antisera raised against the recombinant OvGST1 and OvGST2. The strongest immunogold staining for OvGST1 was identified in the body wall of adult worms, especially in protuberances of the cuticle which lie in pouches of the hypodermis and in the outer zone of the syncytial hypodermis, where the external plasma membrane forms series of lamellae. Gold particles were also observed on the epicuticle of the adults and in the region of the border between the cuticle and hypodermis of microfilariae. The larval stages L1, L2, and infective L3 were also immunopositive for OvGST1. There was no specific labeling in the longitudinal musculature, the intestine, or the uterine wall of the adult worm. In contrast to the results for OvGST1, immunogold labeling for OvGST2 was observed throughout the whole hypodermal cytoplasm. The epithelial cells of the uterine wall showed moderate labeling. These ultrastructural immunolocalization results are consistent with the molecular characterization of both enzymes, indicating that OvGST1 is secreted out of the hypodermis into the cuticle and is acting at the host-parasite interface, while OvGST2 functions as an intracellular cytosolic housekeeping enzyme.     

Developmental changes in intracellular calcium regulation in rat cerebral cortex during hypoxia

During the first weeks of life, injury to the central nervous system caused by brief periods of oxygen deprivation greatly increases. To investigate possible causes for this change, the effects of hypoxia or application of the excitatory neurotransmitter glutamate on intracellular calcium ([Ca2+]i) and ATP were studied in rat cerebrocortical brain slices. [Ca2+]i was measured fluorometrically with the indicator Fura-2. Hypoxia (95% N2/5% CO2) or 100 microM sodium cyanide produced gradual elevations in [Ca2+]i and ATP depletion in slices from rats < 2 weeks old, but rapid changes in older rats. After 20 min, [Ca2+]i in adult slices exposed to cyanide was 1,980 +/- 310 nM; in day 1-14 animals, it was 796 +/- 181 nM (p < 0.05). Combination of cyanide and a glycolytic inhibitor (iodoacetate) rapidly elevated [Ca2+]i and depleted ATP in all age groups. Energy utilization during anoxia, assessed by measuring ATP fall in cyanide/iodoacetate-treated brain slices, increased with age. Elevations in [Ca2+]i caused by application of 500 microM glutamate increased 240% from days 1-2 to day 28, but ATP loss caused by glutamate did not change with age. The N-methyl-D-aspartate antagonist MK-801 delayed calcium entry during the initial 5-7 min of hypoxia or cyanide in rats < 2 weeks old. We conclude that anaerobic ATP production, conservation of energy by reduced ATP consumption, and reduced sensitivity to glutamate contribute to delaying elevation in [Ca2+]i in neonatal rat brain during hypoxia.     

The kinetics of extracellular potassium changes during hypoxia and anoxia in the cat cerebral cortex

Extracellular potassium activity, [K+]0, was continuously measured using potassium specific microelectrodes in the cerebral cortex of cats before and after hypoxic or anoxic insults. Two patterns of [K+]0 increase were seen. A slow, linear rise occurred during hypoxia and hypothermia and was correlated with changes in mean blood pressure (B/P). A fast, complex, exponential rise resembling spreading depression occurred during anoxia and was unassociated with B/P changes. The fall of [K+]0 after reversal of the insult was described by a single exponential function with rate constants from 0.009 to 0.0194 sec-1. It is suggested that the linear rise is primarily a result of sodium pump inhibition and that the exponential rise is due to a superimposed sudden increase in cell membrane permeability perhaps secondary to transmitter release. The kinetics of the fall of [K+[0 is consistent with the normalization of the sodium and potassium gradients across the cell membranes secondary to Na+-K+ATPase activity.     

Astroglial changes in the cerebral cortex of AIDS brains: a morphometric and immunohistochemical investigation

Sutureless phacoemulsification with implantation of a 7-mm PMMA intraocular lens was performed through a modified scleral tunnel in 100 consecutive patients. This was done to minimize postoperative astigmatism while retaining the advantages of implanting intraocular lenses with large optics. Visual and keratometric results and complications are reported after completion of a follow-up period of 6 months for the first 30 patients. Average uncorrected visual acuity improved from 0.13 preoperatively to 0.30 as early as 1 week postoperatively. Average best-corrected visual acuity improved from 0.23 before surgery to 0.51 as early as 1 week after surgery. No significant changes in visual acuity were recorded thereafter. The absolute value of keratometric astigmatism was not increased significantly at any postoperative examination time. The induced cylinder (Jaffe and Clayman) shifted from -1.27 D x 166 degrees at 1 week to 1.18 D x 91 degrees at 1 month postoperatively without further relevant changes thereafter. Endothelial cell loss did not differ from that reported by other authors after conventional cataract surgery. Corneal thickness was not increased significantly at any postoperative examination time. Implantation of intraocular lenses with large optics through a scleral tunnel allows quick visual rehabilitation as well as early stability of refraction.     

The HIV-1 gp120 causes ultrastructural changes typical of apoptosis in the rat cerebral cortex

We used transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labelling (TUNEL) techniques to study the neuropathological effects of intracerebroventricular (i.c.v.) injection of recombinant HIV-1 gp 120 in rats. In brain cortical tissue sections from rats treated with a single daily dose of gp120 (100 ng day-1 for 7 or 14 consecutive days) TEM analysis showed chromatin compaction and marginalization along the inner surface of the nuclear envelope followed by masses of condensed chromatin, ultrastructural signs demonstrating the occurrence of apoptotic cell death. These effects were paralleled by in situ DNA fragmentation, as revealed by application of TUNEL technique to cryostat brain tissue sections from rats treated likewise with the viral coat protein. In no instance was apoptosis seen in the brain cortex of control rats. The present data demonstrate that gp120 given i.c.v. produces apoptosis in the neocortex of rats.     

Hemisphere dominance of the cerebral cortex

An outbreak of erythema infectiosum (fifth disease) occurred in a North Carolina elementary school. Because rubella virus has been implicated as a possible cause of some cases of erythema infectiosum, we conducted an investigation to determine if the children were infected with rubella virus and to learn whether or not rubella virus vaccination prevents the disease. Throat swabs were obtained for viral isolation from 20 children with erythema infectiosum and from 25 healthy classmates; questionnaires were completed for 617 of the school's 817 students. One hundred fifty children (24%) reported having an acute exanthematous illness during the study period, and 45% of the ill children had one or more household contacts with a similar rash. No viruses were recovered from the children, and a history of rubella vaccination did not affect the risk of developing erythema infectiosum.     

Neurotransmitter receptors in the developing cerebral cortex

This review deals with several aspects of neurotransmitter receptor development in the primate cerebral cortex. It describes the presence of multiple neurotransmitter receptors in the transient zones of the fetal cerebral wall. These zones are involved in the production and migration of cortical neurons and the establishment of appropriate innervation of the cortex. It also suggests functions that neurotransmitter receptors may perform in these embryonic zones. In addition, this review shows that a remarkable diversity of neurotransmitter receptors develops concurrently in disparate areas of the primate cerebral cortex and discusses the implications of this finding on our understanding of the general principles underlying development of the cerebral cortical circuitry. Finally, it speculates on factors that may be involved in regulation of neurotransmitter receptor development in the primate cerebral cortex.     

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.     

Neuropsychology and pathology of the cerebral cortex

In all clinics we are faced with questions about certain aspects of cerebral dominance. We consider first the problem of recognition of faces where the right hemisphere plays a leading role. However, the disorders manifesting that function appear only bilateral lesions. This suggests that the left hemisphere participates in this process. The reception of language raises a problem which is analogous with the preceding: we propose the participation of both hemispheres in this activity: the left hemisphere is dominant in the analysis of phonemes and syntax, the right hemisphere seems implicated above all in the processing of prosodic aspects--in particular intonations and individual features of the voice.     

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.     

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