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Spread of MHV-JHM from nasal cavity to white matter of spinal cord. Transneuronal movement and involvement of astrocytes.

C57B1/6 mice infected intranasally with mouse hepatitis virus, strain JHM (MHV-JHM) develop hindlimb paralysis with histological evidence of demyelination several weeks after inoculation. Virus must spread from the site of inoculation, the nasal cavity, to the site of disease, the white matter of the spinal cord. It has been shown previously that after intranasal inoculation, virus enters the brain via the olfactory nerve and spreads to infect many of its neuroanatomic connections within the central nervous system (CNS). In this report, it is shown that virus infecting the spinal cord is first detected in the gray matter, with spread occurring to the white matter soon thereafter. Astrocytes are heavily infected during the process of spread from the gray to the white matter of the spinal cord. Since astrocytes are in intimate contact with neuronal synapses and are themselves connected via gap junctions, these results suggest that astrocytes may be a conduit for the spread of virus in these mice. Astrocytes provide factors for the proliferation and survival of oligodendrocytes, and widespread infection of these cells might contribute to the demyelinating process eventually observed in these mice. Additionally, since virus first appears at specific locations in the spinal cord, it should be possible to determine the source of the virus infecting the cord. While the results are not definitive, the data are most consistent with virus spreading from the ventral reticular formation to the gray matter of the cervical spinal cord.

Animals↗

Protein kinases in the locus coeruleus and periaqueductal gray matter are involved in the expression of opiate withdrawal.

The aim of this study was to evaluate the role played in the behavioral expression of morphine withdrawal syndrome by protein kinases in the locus coeruleus and the periaqueductal gray matter. Two different families of specific protein kinases have been investigated: serine/threonine and tyrosine kinases. Rats were implanted with cannulas into both the lateral ventricle and the locus coeruleus or the periaqueductal gray matter. Physical dependence was induced by chronic peripheral administration of morphine (from 7 to 30 mg/kg) and withdrawal syndrome was precipitated by injection of naloxone (2 micrograms) into the lateral ventricle. The administration of the serine/threonine kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, H7 (1, 3, 10, and 30 nmol per side) into the locus coeruleus induced a strong attenuation of morphine withdrawal behavior. Signs related to the motor component of abstinence, such as jumping, rearing, and hyperactivity, were the most severely reduced. However, this effect was not dose-dependent, and the response was almost the same with all the doses used. A similar attenuation was observed after the injection of H7 (1, 3, and 10 nmol per side) into the periaqueductal gray matter, but in this case motor signs were less strongly reduced and a larger number of signs were modified, mainly when using the highest dose. The administration of the tyrosine kinase inhibitor 2-hydroxy-5-[N(2,5-dihydroxyphenyl)methyl]amino]-benzoic acid 3-phenylpropyl ester, KB23 (0.3, 1, and 3 nmol per side) into the locus coeruleus or the periaqueductal gray matter had no effect on the withdrawal syndrome behavior, except on teeth chattering. These results suggest that in the locus coeruleus and in the periaqueductal gray matter, serine/threonine kinases are implicated in the behavioral expression of morphine abstinence. In these brain structures, tyrosine kinases appear not to be involved.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Demonstration of neurofibrillary tangles and neuropil thread-like structures in spinal cord white matter in parkinsonism-dementia complex on Guam and in Guamanian amyotrophic lateral sclerosis.

This report concerns the demonstration and distribution of neurofibrillary tangles (NFTs), immunoreactive neuropil thread-like structures and dots in the spinal cord gray and white matter of six patients with parkinsonism-dementia complex on Guam and five patients with Guamanian amyotrophic lateral sclerosis (ALS). A monoclonal antibody to Alzheimer NFTs was used. NFTs were found in the spinal cord gray matter and white matter and all patients had immunoreactive neuropil thread-like structures and dots in the gray matter as well as in the white matter. They were particularly numerous in the lateral funiculus of patients with Guamanian ALS.

Amyotrophic Lateral Sclerosis↗

Decrease in nerve fibres in cerebral white matter in progressive subcortical vascular encephalopathy of Binswanger type. An electron microscopic study.

To study white matter changes in the frontal lobes and to investigate the histopathological basis for the dementia in progressive subcortical vascular encephalopathy (PSVE), the frontal white matter was examined by electron microscopy in seven cases with PSVE, and compared with that in a control group and in cases with senile dementia of Alzheimer's type (SDAT). The number of nerve fibres per unit selected area of the white matter was significantly less in PSVE compared with that in the control group or in SDAT. Nerve fibres in PSVE had a tendency to have thinner myelin sheaths than in the control group or in SDAT, but the difference was not significant. The pallor of the frontal white matter in PSVE is mainly based on the loss of nerve fibres, and may be in part based on the thin myelin sheaths. The dementia in PSVE is probably related to the loss of nerve fibres in the cerebral white matter.

Aged↗

Spatial data analysis in the quantitative assessment of cerebral white matter pathology on MRI in HIV infection.

This study was carried out using MRI (proton density--and T2-weighted) on 16 HIV-negative controls, 9 symptom-free HIV-positive patients and 25 with CDC IV HIV disease. The studies from this last group had previously been allocated by a radiologist to the following categories: 8 with focal mass lesions and normal-appearing white matter; 9 with diffuse encephalopathy (high signal on T2-weighted images, affecting most or all of the white matter) and 8 with patchy encephalopathy (high signal affecting only one or two areas within the white matter). Moran's I, a statistic of spatial autocorrelation, was calculated for the grey-scale values of a sampled pixel array from a central white matter region of each of the images. All values of Moran's I calculated in this study showed a large positive excess over the expected value under randomisation, indicating highly significant positive auto-correlation in the spatial arrangement of the grey-scale values. On T2-weighted images a statistically significant increase in the mean value of Moran's I, compared with controls, was found in the diffuse encephalopathy group, indicating that quantifiable changes in the spatial autocorrelation of pixel data can be related to recognised qualitative changes in the appearance of white matter in subjects with HIV disease. A lesser, but significant, rise in the mean value of Moran's I was also found in the focal mass lesion group, suggesting that changes in spatial autocorrelation may indicate pathological change in advance of qualitative MRI changes.

AIDS Dementia Complex↗

Functioning heterotopic grey matter? Increased blood flow with voluntary movement and sensory stimulation.

A 66-year-old woman with a right hemiplegia due to cerebral haemorrhage was found to have heterotopic grey matter in the left frontal and right frontal and parietal lobes. She had no neurological disturbance prior to the haemorrhage. Regional cerebral blood flow (rCBF) was measured by xenon-CT (Xe-CT) in the zones of heterotopic grey matter during voluntary movement and sensory stimulation of her left limbs. During voluntary movement, rCBF increased markedly in the heterotopic grey matter of the frontal lobes and the overlying cortex. During sensory stimulation, rCBF increased in the right parietal heterotopic grey matter and the overlying cortex. This strongly suggests that the heterotopic grey matter is functional.

Aged↗

MRI and pathological examination of post-mortem brains: the problem of white matter high signal areas.

We examined 21 brains from individuals more than 65 years of age by MRI and neuropathological methods to study the frequency and morphology of white matter changes. There were 16 brains from neurologically normal subjects (Group 1) while the remaining 5 (Group 2) had neurological disturbances. In Group 1 MRI showed high signal areas in the periventricular white matter in 12 brains and in the deep white matter in 9. All had focal areas, with confluent zones in 4; 3 cystic infarcts were also detected. Neuropathology in this Group showed periventricular changes of variable extent in all cases, vacuolated myelin around the perivascular spaces in 14 and degenerate myelin in 4. Macroscopic inspection showed 3 cystic lacunar infarcts, while areas of recent infarction were present on histology in 2. Four of the Group 2 brains had periventricular MRI changes; high signal areas in deep white matter were focal in 2 and confluent in 1. Cystic infarcts were detected in 3 cases. Neuropathology showed periventricular changes in all the brains; in 4 myelin around the perivascular spaces was vacuolated while degenerate myelin was demonstrated in 1. There were also old (1) and recent (2) lacunar infarcts. High signal areas in the white matter thus have different histological backgrounds but only in a minority of cases do they seem to be of pathological significance and, as a rule, they are not related to the presence of neurological disturbances. Correlative MRI-neuropathological studies are helpful for characterising abnormalities detected by techniques, like MRI, which are sensitive but not very specific.

Aged↗

Alterations in the activity of phospholipases A2 in postmortem white matter from patients with multiple sclerosis.

Activities toward arachidonyl-labelled phospholipase A2 substrates were assayed in fractions of white matter and cerebral cortex from control subjects and in fractions of demyelinated plaque, normal-appearing white matter and cerebral cortex from subjects who died with multiple sclerosis. Membranous activity at pH 8.6 in the presence of Ca2+, characteristic of 14 kDa "secretory" phospholipase A2, in either multiple sclerosis white matter or cortex did not differ from controls, whereas membranous activity at pH 4.5 in the absence of added Ca2+, characteristic of lysosomal enzymes was increased over controls in both plaque and normal-appearing white matter but not cerebral cortex. Activity in the cytosol fraction, at pH 8.6 in the presence of Ca2+ and glycerol characteristic of the "cytosolic" 85 kDa enzyme was decreased by greater than 50% in both white matter and cortex samples from multiple sclerosis subjects. Immuno-precipitation and -blotting confirmed that the deficient activity was largely attributable to the 85 kDa enzyme although the enzyme protein was not similarly reduced.

Arachidonic Acid↗

Brain-specific hyaluronate-binding protein. A product of white matter astrocytes?

The distribution of glial fibrillary acidic (GFA) protein and hyaluronectin, a hyaluronate-binding protein isolated from human brain, was compared in brain, spinal cord and optic nerves of pigs and dogs by indirect immunofluorescence with monoclonal antibodies. In spinal cord white matter the localization of the two proteins was similar, both antigens forming a mesh surrounding myelinated axons. A similar distribution of the two proteins was also observed in the periventricular glia as well as in the glia limitans of spinal cord and optic nerves. Cerebral white matter was hyaluronectin-positive, but the GFA-positive stellate astrocytes did not stain with hyaluronectin antibodies in this location. Hyaluronectin antibodies did not stain grey matter, the granular layer of the cerebellum excepted. The astrocytes identified with GFA antibodies in hyaluronectin-negative grey matter were: the fibrous astrocytes forming the glia limitans on the surface of the cerebral hemispheres; the protoplasmic astrocytes of cerebral isocortex and basal ganglia; the fibrous astrocytes of cerebral allocortex (hippocampus); Bergmann radial glia in the molecular layer of the cerebellar cortex; and fibrous astrocytes of spinal cord anterior and posterior horns. It is concluded that the hyaluronectin fraction reacting with the monoclonal antibodies is a brain-specific protein probably produced by white matter astrocytes. We propose to call this fraction brain-specific hyaluronectin, to be distinguished from other fractions reacting with polyclonal antibodies and with different localizations.

Animals↗

Creutzfeldt-Jakob disease with severe involvement of cerebral white matter and cerebellum.

We describe a patient with Creutzfeldt-Jakob disease (CJD) of the ataxic and panencephalopathic type. Postmortem examination revealed the characteristic lesions of CJD in the grey matter and profound white matter involvement was seen with immunocytochemical techniques. Ultrastructural white matter lesions were identical to those described in experimentally transmitted CJD. There was marked loss of cerebellar granule cells with virtual disappearance of parallel fibres, but Purkinje cells were only slightly reduced. Electron microscopic studies revealed extensive degenerative changes including cytoplasmic vacuoles in both cell types. Silver methods disclosed massive impregnation of white matter and striking abnormalities of Purkinje cells consisting of hypertrophy and flattening of thick dendritic branches, reduction in the number of terminal branchlets, segmentary loss of spines and polymorphic spines. These findings show the extensive involvement of all three cerebellar cortical layers and the reactive plasticity of Purkinje cells to deafferentiation. They favour the hypothesis that demyelination represents a primary lesion of the white matter.

Brain↗

Theoretical situation of brain white matter tracts evaluated by three-dimensional MRI.

An accurate knowledge of cerebral anatomy is important in order to evaluate the precise location of a cerebral lesion. Cortical structures are identified by knowledge of the adjacent gyri and sulci; however, white matter tracts are difficult to differentiate from one another due to the lack of clear anatomic landmarks. Therefore, even if MRI shows obvious white matter abnormalities, in some cases it is difficult accurately to localize the lesion. The purpose of this study is to evaluate the location of the main white matter tracts by using three-dimensional MR imaging. MRI study was performed by 1.5 Tesla (Signa: General Electric). Computer assisted analysis with Voxtool software (General Electric) was used to generate both surface brain and tomographic images. The exact anatomic basis of white matter signal abnormalities is important when analyzing patients with disconnective syndromes or neuropsychological deficits such as conduction aphasia, visuospatial deficit etc. This preliminary attempt at constructing a three-dimensional MRI white matter atlas of the brain may be helpful for evaluating the anatomico-clinical correlations in these patients, and also as teaching materials for the clinical (neurologic, neurosurgical), anatomic and radiographic disciplines.

Adult↗

Autoprotective mechanisms in the CNS: some new lessons from white matter.

Anoxia/ischemia in the CNS is a common and devastating phenomenon. It is possible that the best hopes for protection against anoxic/ischemic injury may involve recruiting and/or augmenting any autoprotective systems that evolution has provided for the CNS. We describe here the existence of such an autoprotective system present in CNS white matter. White matter is both well suited to studying extrasynaptic systems, such as the system we describe here, and is a highly appropriate target for research into anoxic-ischemic injury in its own right. We show that white matter contains functional GABAB and adenosine receptors that respond to an anoxic efflux of GABA and adenosine by recruiting a convergent intracellular mechanism involving protein kinase C (PKC). The net result of this receptor-mediated cascade is an increase in resistance to anoxia, which presumably allows CNS white matter to tolerate better a common class of ischemic events that are located solely in white matter and that comprises approximately 25% of all strokes seen clinically.

Animals↗

Grey matter heterotopia: an unusual association of intractable epilepsy.

Heterotopic grey matter is an abnormality of neuronal migration that has been reported in association with refractory epilepsy. In this study we reviewed the magnetic resonance (MR) imaging records of all patients undergoing MR scanning for evaluation of intractable epilepsy and identified sixteen patients who had grey matter heterotopia. The distribution of the grey matter heterotopia was periventricular in 9 patients, laminar in 3 and was in a "band" form in 4 patients. Congenital anomalies associated with grey matter heterotopia in this study included polymicrogyria in one patient and absence of the corpus callosum in 2 patients. Grey matter heterotopia is an important MR finding in patients with intractable epilepsy.

Adolescent↗

Hunting for Dark Matter particles with new detectors.

Although first hints of the existence of Dark Matter were observed by the Swiss astronomer Zwicky already in the 1930s, only in recent years has it become known that the universe, in fact, is dominated by particles whose nature is almost unknown and which have never been directly observed. Meanwhile, as the existence of these particles is postulated not only by astronomy, but also cosmology and theoretical particle physics, there is significant effort to detect them in a laboratory experiment and determine their physical properties. However, as the interaction rate between Dark Matter particles and ordinary matter is extremely low, detectors have to be extremely sensitive. Low temperature detectors have been available for more than a decade and have now reached the highest sensitivity for direct Dark Matter detection. In this article, we give a short overview of observational results that suggest the existence of Dark Matter particles and what physicists have learned so far about their properties. The main focus is on the experimental challenges and effort for their direct detection.

Astronomical Phenomena↗

Magnetization transfer changes of grey and white matter in Parkinson's disease.

Since the attempt to evidence structural brain damage in Parkinson's disease (PD) by conventional magnetic resonance imaging (MRI) is usually disappointing, we have investigated whether the magnetization transfer ratio (MTR) can reflect changes in grey and white matter of PD patients. MTR was quantified in 44 regions of interest (ROIs) in both grey and white matter of 11 non-demented PD patients, ranging from 2 to 4 on the Hoehn and Yahr Scale, and eight age-matched healthy subjects. MTR differences between patients and controls were found in the supratentorial white matter and in the brainstem. In particular, lower MTR values were found in the paraventricular white matter of PD patients (p<0.05) while no differences were observed in corpus callosum, frontal, parietal, occipital lobes or centrum semiovalis. Lower MTR values were found in substantia nigra (p<0.001), red nucleus (p<0.05) and pons (p<0.05) of the patient group. No differences were discovered in basal ganglia and thalamus. These findings suggest that MTR measurements in the paraventricular white matter and brainstem may help to recognize a marker for probable PD.

Aged↗

Anterior temporal white matter lesions in myotonic dystrophy with intellectual impairment: an MRI and neuropathological study.

We studied 12 patients with myotonic dystrophy using MRI and the Mini-mental state examination (MMSE), to see it specific MRI findings were associated with intellectual impairment. We also compared them with the neuropathological findings in an autopsy case of MD with intellectual impairment. Mild intellectual impairment was found in 8 of the 12 patients. On T2-weighted and proton density-weighted images, high-intensity areas were seen in cerebral white matter in 10 of the 12 patients. In seven of these, anterior temporal white-matter lesions (ATWML) were found; all seven had mild intellectual impairment (MMSE 22-26), whereas none of the four patients with normal mentation had ATWML. In only one of the eight patients with intellectual impairment were white-matter lesions not found. Pathological findings were severe loss and disordered arrangement of myelin sheaths and axons in addition to heterotopic neurons within anterior temporal white matter. Bilateral ATWML might be a factor for intellectual impairment in MD. The retrospective pathological study raised the possibility that the ATWML are compatible with focal dysplasia of white matter.

Adult↗

Effects of benzo(a)pyrene and size of organic matter particles on bioaccumulation and growth of Asellus aquaticus.

The effects of sediment-bound toxicants to aquatic invertebrates may vary due to differences in bioavailability, food quality, or food structure. The equilibrium partitioning theory (EPT) assumes that organic matter content of sediments and not structure of organic matter is relevant for biological effects of polycyclic aromatic hydrocarbons. To test this hypothesis effects of benzo(a)pyrene (B(a)P) and size of sediment organic matter particles on the bioaccumulation and growth of the waterlouse Asellus aquaticus were studied in laboratory microcosms. Sediments and A. aquaticus were both sampled in an unpolluted, spring-fed pond. The sampled sediment was divided into two portions. From one portion the size of the organic matter particles was mechanically reduced. One set of each sediment fraction (fine and coarse) was spiked with B(a)P and incubated for 3 weeks resulting in a concentration of 70 mg B(a)P per kg sediment. Bioassays of 32 days were performed in a 2 x 2 factorial design with four replicas of each treatment. The results showed that the growth of A. aquaticus was mainly influenced by the size of organic matter particles. Growth was significantly less (27%) on finer sediments than on coarser sediments. The increase in length was 9-14% lower in the spiked sediments, but this difference was not significant. The reduced growth of A. aquaticus on finer sediments may be due to a change in the availability and/or quality of food together with a change in feeding behavior. The coarse and fine spiked sediment types did not differ significantly with respect to the sediment water partition coefficient, the organic carbon water partition coefficient, and the bioconcentration factor. In contrast, the biota to sediment accumulation factors were significantly 15% higher in the cosms with coarse sediments than in cosms with fine sediments. However, this difference is too small to conflict with EPT.

Animals↗

Localized (1)H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis.

The brain water fraction (R), the brain water transverse relaxation time (T2), the atrophy index (alpha) and the absolute concentration of the principal brain metabolites (NAA, Cho and Cr) were measured by localized proton magnetic resonance spectroscopy in the occipito-parietal cortex (mainly gray matter) of 15 relapsing-remitting (R-R) multiple sclerosis (MS) patients, 15 secondary progressive (SP) MS patients and 8 healthy subjects. Significantly lower values of N-acetylaspartate (NAA), creatine (Cr) and the NAA/Cr ratio in the occipito-parietal cortex were detected in SP MS patients than in R-R MS and control subjects (p < 0.01). Moreover, MS patients showed shorter T2 water relaxation times and reduced brain water fraction compared with controls. Higher atrophy indices were also detected in the mainly occipito-parietal gray matter of MS patients, particularly in those with the progressive form. These findings suggest that the pathological process in MS is not limited to either white matter lesions or normal-appearing white matter but extends into the cortical gray matter (occipito-parietal), particularly in the progressive form of the disease. This can involve changes in neural metabolism or neural shrinkage and neuron loss. The significant increase in atrophy indices could be the expression of the relatively higher cerebrospinal fluid signal from the occipito-parietal cortex, even in the absence of obvious cortical atrophy.

Adult↗