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Bilateral cavernous sinus thromboses and intraorbital abscesses secondary to Streptococcus milleri.

PURPOSE: To report the first case of bilateral cavernous sinus thromboses and bilateral intraorbital abscesses secondary to Streptococcus milleri. STUDY DESIGN: Single interventional case report. INTERVENTION AND TESTING: The findings of the ophthalmic evaluation, radiographic imaging, medical and surgical intervention, specimen cultures, and clinical course were analyzed. RESULTS: A 17-year-old female had bilateral proptosis, decreased vision in the left eye, and altered mental status at presentation. An orbital compartment syndrome developed in the left eye and purulent material was present after lateral canthotomy, suggestive of an intraorbital abscess. Magnetic resonance imaging (MRI) scans revealed bilateral cavernous sinus thromboses, and subsequent computed tomographic (CT) scans revealed bilateral intraorbital abscesses in the setting of acute ethmoid and sphenoid sinusitis. Antibiotic treatment and surgical drainage of the orbital abscess and sinuses was performed, and specimen cultures revealed S. milleri. After surgery, the patient experienced hearing loss and a right internal capsule infarct, in addition to complete vision loss in the left eye. A second intraorbital abscess developed in the right eye and was drained surgically. The vision remained 20/20. CONCLUSIONS: Streptococcus milleri is a virulent organism with a propensity to form abscesses in multiple areas of the body and should be considered as a possible etiologic agent in abscess formation of the orbit and cavernous sinus thrombosis.

Abscess↗

Migration patterns and phenotypic differentiation of long-term expanded human neural progenitor cells after transplantation into the adult rat brain.

We have examined long-term growth-factor expanded human neural progenitors following transplantation into the adult rat brain. Cells, obtained from the forebrain of a 9-week old fetus, propagated in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor were transplanted into the striatum, subventricular zone (SVZ), and hippocampus. At 14 weeks, implanted cells were identified using antisera recognizing human nuclei and the reporter gene green fluorescent protein. Different migration patterns of the grafted cells were observed: (i) target-directed migration of doublecortin (DCX, a marker for migrating neuroblasts)-positive cells along the rostral migratory stream to the olfactory bulb and into the granular cell layer following transplantation into the SVZ and hippocampus, respectively; (ii) non-directed migration of DCX-positive cells in the grey matter in striatum and hippocampus, and (iii) extensive migration of above all nestin-positive/DCX-negative cells within white matter tracts. At the striatal implantation site, neuronal differentiation was most pronounced at the graft core with axonal projections extending along the internal capsule bundles. In the hippocampus, cells differentiated primarily into interneurons both in the dentate gyrus and in the CA1-3 regions as well as into granule-like neurons. In the striatum and hippocampus, a significant proportion of the grafted cells differentiated into glial cells, some with long processes extending along white matter tracts. Although the survival time was over 3 months in the present study a large fraction of the grafted cells remained undifferentiated in a stem or progenitor cell stage as revealed by the expression of nestin and/or GFAP.

Animals↗

Neurochemical heterogeneity of the thalamic reticular and perireticular nuclei in developing rabbits: patterns of calbindin expression.

The thalamic reticular nucleus (TRN) forms an essential part of the circuits that link the thalamus to the cortex, whereas the perireticular thalamic nucleus (PRN) consists of scattered neurons that are located in the internal capsule, in close relation to the TRN. A common feature of these nuclei in different species is the immunoreactivity for some calcium binding proteins with a developmental pattern of expression. In the present study, sections from rabbits at different ages were examined to determine the calbindin (CB) expression in the developing TRN and PRN at the first stages of development. These CB-expressing cells constitute an important subpopulation of neurons in the caudal half of the developing TRN. In the adult, there are still positive CB somata in the middle and caudal halves of the nucleus. In the PRN, where the developmental pattern of CB expression has not been described before, the number of CB perireticular cells decreases progressively. Our results, together with previous data in the rabbit suggest the existence of remarkable neurochemical heterogeneity in the TRN and PRN of the rabbit.

Animals↗

Effects of gestational methylmercury exposure on immunoreactivity of specific isoforms of PKC and enzyme activity during post-natal development of the rat brain.

Protein kinase C (PKC)-mediated phosphorylation has been implicated in neuronal growth and differentiation [R.S. Turner, R.L. Mazzei, G.J. Raynor, P.R. Girard, J.F. Kuo, Proc. Natl. Acad. Sci. U.S.A., 81 (1984) 3143-3147.]. We examined effects of gestational exposure to the neurotoxicant, methylmercury (CH3Hg), on the developmental profile of immunoreactivity (IR) for alpha, beta, gamma and epsilon PKC isoforms and cytosolic PKC activity. Long-Evans dams were dosed on gestational days (GD)6-15 (p.o.) with 0, 1, or 2 mg kg-1 day-1 CH3Hg dissolved in saline. Pups were sacrificed and perfused with buffered paraformaldehyde on post-natal days (PND) 1, 4, 10, 21, 45 and 85. The brains were sectioned sagittally, stained immunohistochemically, and examined throughout the medial to lateral extent. IR in neuronal cell bodies for PKC isoforms alpha, beta, gamma, and epsilon was densest in the olfactory bulb, hippocampus, shell of the inferior colliculus, pons, cerebral, piriform, and cerebellar cortex, whereas axonal staining was prominent in the brainstem, internal capsule, corpus callosum, anterior commissure, fornix and olfactory tract. In controls, the PKC alpha and epsilon IR was highest on PND1-4, decreased dramatically by PND10, and decreased further by PND21. In the neonate, the regional and cellular distributions of alpha and epsilon IR were similar. The PKC gamma IR was greater at post-weaning ages (PND21-85) with the greatest regional density apparent in the hippocampus, cortex, and cerebellum. Only the highest dose of CH3Hg (2 mg kg-1 day-1; GD6-15) produced a persistent decrease in regional alpha and epsilon, but not beta or gamma IR during the post-natal period. These regional and time-dependent changes in PKC isoforms were complemented by the examination of PKC activity in cortex, olfactory bulb, cerebellum and brainstem. Cytosolic PKC activity increased from PND1 to 10 in cortex, olfactory bulb, and cerebellum. On PND21, PKC activity decreased in the cortex and olfactory bulb, but remained high in the cerebellum. By contrast, PKC activity in the brainstem was highest on PND1 and 4 and decreased dramatically by PND21. CH3Hg (2 mg kg-1 day-1) significantly decreased PKC activity on PND1 and 4 in the cortex. The present results characterize the cellular and regional ontogeny of PKC isoenzymes alpha, beta, gamma and epsilon, and indicate that developmental exposure to CH3Hg can alter the ontogeny of specific isoforms and regional PKC activity.

Animals↗

Expression of serotonin transporter protein in developing rat brain.

Serotonin transporter (5-HTT), a transmembrane protein, has been shown in adult brain to be distributed not only on synaptic terminals but to a great extent on axons as well. Here we report the ontogeny of 5-HTT and its relationship with serotonin (5-HT) neurons using established 5-HTT and 5-HT antibodies. Both 5-HTT- and 5-HT-immunostaining (-im) appear in 5-HT neurons at embryonic day 12 (E12) in rostral raphe nuclei (RRN). Soon after appearing, 5-HTT-im is highly expressed on axons, similar to adult expression. However, in contrast to adult, 5-HTT-im also outlines the soma-dendrites. Rich 5-HTT-im appears along the entire length of projecting axons, extending to the growth tip. In the next 2 days, intensive 5-HTT-im axons from RRN travel a course preferentially in the floor plate and later, the medial forebrain bundle trajectory. A group of new 5-HT-im neurons and 5-HTT-im axons appear at E13 in caudal raphe nuclei. At E16-18, taking the exact trajectory course of 5-HT axons, 5-HTT-im axons reach ganglionic eminence, olfactory bulb, and cortex and disperse into many brain regions in E18-20. No 5-HTT-im cell bodies were seen in nigral, locus ceruleus, or hypothalamus. However, the transient expression of 5-HTT on non-serotonergic system was seen in cortical and striatal neuroepithelia at E12 and sensory thalamic pathways at P0-P10. Prominent 5-HTT-im fibers in thalamocortical bundles project from sensory thalamic nuclei through reticular nucleus, internal capsule bundle and form barrels in somatosensory cortices. No 5-HTT-im was seen in glia-like cells using currently available antibody. These observations indicate that 5-HTT is: (a) associated preferentially with 5-HT neurons in brainstem, (b) temporally co-expressed with 5-HT in 5-HT neurons, (c) expressed on axons prior to synaptical sites at target neurons, which strongly indicates a volumic (extrasynaptic) transmission, (d) expressed in non-5-HT neurons within a specific window, which may affect the development of the systems "borrowing" the 5-HT. The early appearance of 5-HTT may also endow functionality as well as vulnerabilities of 5-HT, sensory thalamic, and cortical neurons to 5-HTT targeting drugs during pregnancy and after birth.

Animals↗

Gastric mucosal erosion produced by NMDA microinfusions in the lateral hypothalamus: effect of selective knife cuts.

Bilateral infusions of N-methyl-D-aspartate (NMDA) into the lateral hypothalamus (LH) produce gastric erosions in rats. The present study attempted to determine the neural pathways that mediate this effect. In order to interrupt axonal transmission, knife cuts (KC) were made in different planes adjacent to the LH. In separate groups of rats, KC were made anterior, posterior or lateral to the LH just prior to bilateral NMDA infusions (20 micrograms/microliter). The incidence of gastric erosions was measured 24 h after NMDA infusions. Animals receiving sham KC and infused with NMDA exhibited significantly more gastric erosions than those infused with vehicle. Lateral parasagittal KC blocked the occurrence of gastric erosions produced by NMDA, whereas anterior coronal KC significantly increased the incidence of erosions produced by NMDA. Posterior coronal KC did not alter the incidence of gastric erosions produced by NMDA infusions into the LH. These results suggest that intrinsic LH neurons with gastric function project axons laterally and probably descend through the internal capsule to brainstem medullary nuclei. The results of the anterior KC suggest that the LH sends and/or receives inhibitory projections from neural structures (possibly the amygdaloid complex) anterior to the plane of the KC.

Animals↗

Cell migration from the ganglionic eminence to the neocortex investigated by labeling nuclei with UV irradiation via a fiber-optic cable.

Recent studies have shown that the ganglionic eminence is one of the sources of tangentially migrating cells in the developing neocortex. Since the migration of the DiI-labeled cells from the ganglionic eminence to the neocortex was not monitored by videomicroscopy in these reports, we devised a novel method to study cell migration in vitro and in vivo. The new method involves ultraviolet (UV) irradiation of the cells through a fiber-optic cable and subsequent identification of the irradiated cells on the basis of the formation of thymine dimers in the nuclei. First, we tested the new method (UV-thymine dimer-labeling method) by applying it to monitor the cell migration of neuronal precursor cells in the rostral migratory stream in the neonatal rat telencephalon. In vitro, UV irradiation for 1 s through the fiber-optic cable resulted in the formation of sufficient thymine dimers as to allow immunohistochemical detection after 6 h of incubation; a significant proportion of the irradiated cells continued to migrate in the same direction and at the same speed as those before irradiation. There was no significant difference in the cell migration distance over 6 h between cells exposed and not exposed to the UV irradiation in vitro. In vivo, this method revealed that three times as many cells in the subventricular zone of the olfactory bulb migrated rostrally as caudally. The new method also allowed us to measure the speed of cell migration, which was estimated to be about 70 microm/h at the maximum in the rostral direction. After these examinations of reliability of the method, we applied it to the rat embryo brain. One day after UV irradiation of the ganglionic eminence, labeled migrating cells were found in the striatum, in the internal capsule, and in the intermediate zone of the neocortex. The observation period of cell migration to the neocortex was extended by the use of a xeroderma pigmentosum group A gene mutant mouse, which lacked an ability to remove thymine dimer from the UV-irradiated nuclei. Two days after the UV irradiation, labeled migrating cells from the ganglionic eminence of the mutant mouse embryos were found both in the cortical plate and in the intermediate zone of the neocortex.

Animals↗

A quantitative evaluation of magnetic resonance image signal changes of the brain in chronic hepatic encephalopathy.

Hyperintensity in the basal ganglia of patients with serious liver disease is a common finding on T1-weighted magnetic resonance images. In this study, we used optical densitometry to quantitatively evaluate the hyperintense magnetic resonance image signal changes in the various regions of the brain of patients with chronic hepatic encephalopathy. The incidence and morphological distribution of the magnetic resonance signal changes were evaluated from T1-weighted magnetic resonance images of the brain from seven non-alcoholic patients and six healthy controls. Significant differences (p < 0.05) between the patient group and controls were found in the limbic system (hippocampus, temporal lobe, cingulate gyrus, and fornix), extrapyramidal system and associated myelinated pathways (lentiform nucleus, tectum, tegmentum, cerebral peduncles, internal capsule and the corpus callosum). No measurable differences were observed in the frontal, parietal, and occipital cortex, or the dorsomedial thalamus. The presence of the high signal intensity changes on T1-weighted magnetic resonance image suggests that characteristics alterations occur in functional regions of the brain in chronic hepatic encephalopathy.

Adolescent↗

Differential distribution of the putative vesicular transporter for acetylcholine in the rat central nervous system.

The organization and distribution of the mRNA for the putative vesicular transporter for acetylcholine (VAChT) was studied in the rat brain by use of digoxigenin-labeled riboprobes and in situ hybridization technology. Signal was observed in all neural regions deduced to contain cholinergic somata on the basis of previous histochemical investigations employing choline acetyltransferase riboprobes and prior immunocytochemical studies with antibodies against choline acetyltransferase. It was absent in areas believed to contain no cholinergic neurons. Anti-sense riboprobes hybridized to the mRNA for the putative VAChT: (a) the projection neurons of the various nuclei of the basal nuclear complex, (b) the local circuit cells of the dorsal and ventral striata, (c) the projection neurons of the mesopontine complex, (d) perikarya in the ventral 2/3 of the medial habenula, (e) the somatic motor and autonomic cells of cranial nerves 3-7 and 9-12, as well as perikarya in the dorsal and ventral cochlear nuclei presumably giving rise to efferent fibers of cranial nerve 8, and (f) the alpha-motor and gamma-efferent motor neurons of the spinal cord. In addition, the mRNA for the VAChT was found in a few somata, probably ectopically located cells of the basal nuclear complex, in the internal capsule, central nucleus of the amygdala, entopeduncular nucleus, and zona incerta. It was also detected in some cell bodies in the reticular part of the substantia nigra, probably the rostral extension of the mesopontine complex, in the parabigeminal nucleus, and around the central canal in the spinal cord but not in cortical, hippocampal, and cerebellar perikarya. It is concluded that, like choline acetyltransferase, the mRNA for the putative acetylcholine vesicular transporter is another specific marker for neurons utilizing acetylcholine as a neurotransmitter. Further investigations of that transporter could have important implications for various diseases involving cholinergic systems, such as Alzheimer's disease.

Acetylcholine↗

Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis.

The purpose of this study is to elucidate changes in mean diffusivity (ADC) and fractional anisotropy (FA) using MR diffusion tensor imaging (DTI) in the central nervous system during normal aging. We studied 50 normal volunteers (30 men, 20 women; mean age 44.8 +/- 14.0; age range, 21-69 years) without disorders affecting the central nervous system. The frontal, parietal white matter, lentiform nucleus, posterior limb of internal capsule, thalamus, genu and splenium of the corpus callosum were selected for investigation. There was no significant difference in ADC or FA between male and female or between the right and left hemisphere. A significant ADC increase with advancing age was observed in frontal white matter (P = 0.010) and lentiform nucleus (P = 0.022). A significant FA decline was found only in the genu of the corpus callosum (P < 0.001) with advancing age. Quantitative diffusion tensor analysis correlate with normal aging and may help in assessing normal age-related changes and serve as a standard for comparison with neurodegenerative disorders.

Adult↗

Putative estrogen receptor beta and alpha mRNA expression in male and female rhesus macaques.

The profound effects of estrogen on different tissues may involve at least two estrogen receptor (ER) subtypes, ERalpha and the recently discovered ERbeta. Where and how the two ER subtypes differentially or cooperatively mediate estrogen actions, however, are still unknown. In this study, we report the cloning of a specific ERbeta cDNA fragment and the expression of ERalpha and ERbeta mRNAs in various endocrine and non-endocrine tissues of male and female rhesus macaques. Total RNA from monkey tissues was isolated and subjected to reverse transcription-polymerase chain reaction (RT-PCR) using human-specific ERbeta primers. A 126 bp RT-PCR product was identified in ovarian tissue and subsequently transfected into pGEM-T vectors for DNA sequencing. The cloned rhesus monkey ERbeta fragment contained a sequence nearly identical to the corresponding sequence in the human (four mismatched nucleotides out of 126). Because complete monkey ERbeta and ERalpha DNA sequences have not been established, the expression of the ERbeta and ERalpha fragments in monkey tissues by RT-PCR reflects 'putative' ERbeta and ERalpha mRNA expression, respectively. Both ERbeta and ERalpha mRNAs were present in male and female reproductive organs, in several endocrine and non-endocrine tissues, and in various regions of the brain, whereas several tissues, including liver, frontal cortex, caudate nucleus, locus coeruleus and cerebellum, expressed only ERalpha message. In some brain regions, i.e. the putamen, internal capsule, hippocampus and paraventricular hypothalamus, the ERbeta fragment was expressed in the female but not in the male. These data suggest that ERalpha mRNA is widely distributed in both female and male tissues, while ERbeta mRNA is more widely distributed in female than in male brain.

Amino Acid Sequence↗

Depression with anosognosia following a left subcortical stroke.

Controversy exists about whether depression following stroke represents a biologically mediated change or a psychological reaction to the deficits. We present a patient with an acute isolated personality change and depression following a lacunar infarct of the left internal capsule, who was unaware of his affective change. His anosognosia for the depression, which was abrupt and not accompanied by cognitive impairments, suggests that post stroke depression, at least in this case, is better explained by a biological than a psychological model.

Aged↗

Adult type of leukodystrophy. Krabbe's disease?

A 24-year-old man developed progressive dementia in seven years. The patient suffered a severe bronchopneumonia and eventually died few days later. Brain coronal sections showed a soft gray-brownish discoloration of white matter of centrum ovale but the subcortical arcuate fibers and the interne capsule were preserved. Microscopically, the white matter showed marked loss of myelin and oligodendrocytes, abundant hypertrophic astrocytes and numerous "globoid cells". The latter showed strong positivity in immunostains for a mouse monoclonal antigalactocerebroside antibody. The presence of these cells in the brain white matter might be the morphological basis to classify the present case as one of Krabbe's Leukodystrophy.

Adult↗

Pediatric brain stem tumor presenting as a pure motor hemiparesis.

The clinical syndrome of pure motor hemiparesis occurs with lacunar lesions in the internal capsule or in the basis pontis in hypertensive adults. It has been described in three patients with brain stem tumors of which two were children. A 3 1/2 years old boy with a brain stem tumor which presented as pure motor hemiparesis is described.

Brain Neoplasms↗

Bilateral ptosis and changes in state of alertness in thalamic infarction.

Uni- or bilateral supranuclear ptosis is known to be caused by cerebral lesion. The exact anatomical cortical and subcortical basis is still undefined. We report a case of a patient developing bilateral ptosis with a left thalamic lesion. The bilateral ptosis was associated with transient changes in the state of alertness. We postulate that the thalamus, especially the anterior region, may have an influential role on the pathway from the cortex via the posterior branch of the internal capsule to the levator palpebrae superioris nuclei.

Arousal↗

In vivo 3D visualization of normal pyramidal tracts in human subjects using diffusion weighted magnetic resonance imaging and a neuronavigation system.

We describe the potential of anisotropic diffusion weighted imaging to visualize the course of large cerebral fiber tracts. Five healthy volunteers were investigated at a field strength of 1.5 Tesla, employing a spin-echo diffusion weighted sequence with gradient sensitivity in six non-collinear directions to visualize the course of the pyramidal tracts. The pyramidal tracts were segmented and reconstructed for three-dimensional visualization. Reconstruction results together with a fusioned high resolution 3D T1 weighted image data set were available in a customized neuronavigation system. Origination in the primary motor cortex, convergence in the centrum semiovale, the posterior limb of the internal capsule, the cerebral peduncles, the splitting at the level of the pons, and the pyramidal decussation were identified in all subjects. Fiber tract maps might have the prospect of guiding neurosurgical interventions, especially when being linked to a neuronavigation system. Other potential applications include the demonstration of the anatomical substrate of functional connectivity in the human brain.

Adult↗

Differences in white matter architecture between musicians and non-musicians: a diffusion tensor imaging study.

Previous studies found structural brain differences between musicians and non-musicians. In order to determine possible differences in white matter architecture, diffusion tensor imaging was performed on five adult subjects with musical training since early childhood, and seven adult controls. The musicians displayed significantly greater fractional anisotropy (FA) in the genu of the corpus callosum, while significantly less FA was found in the corona radiata and the internal capsule bilaterally. Further areas also showed significant differences. We hypothesize that these changes are due to the cognitive and motor effects, respectively, of musical training.

Adult↗

Forebrain white matter in spontaneously hypertensive rats: a quantitative image analysis study.

The volume and the morphology of brain white matter as well as the number and the size of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were investigated in 6-month-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. The volume of frontal and occipital cortex and of hippocampus was decreased in SHR in comparison with normotensive rats, whereas the volume of neostriatum was unchanged. A remarkable decrease of the volume of internal capsule and striosomes, a moderate reduction of that of corpus callosum and no changes of the volume of external capsule and of white matter of hippocampus were also observed in SHR. In SHR the number of astrocytes was higher in the frontal and occipital cortex and in the white matter of the CA1 and CA3 subfields of the hippocampus, but not in the corpus callosum or in the grey matter of the CA1 and CA3 subfields. Staining for myelin did not reveal alterations in single fibre sheath morphology. These findings indicate the occurrence of changes of forebrain white matter in SHR, consisting in the reduction of it without qualitative modifications of myelinated fibres. The development of gliosis apparently not related with changes of volume of white matter was also found.

Animals↗