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PubMed2001

In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease.

Up till now, the study of regional gray matter atrophy in Alzheimer's disease (AD) has been assessed with regions of interest, but this method is time-consuming, observer dependent, and poorly reproducible (especially in terms of cortical regions boundaries) and in addition is not suited to provide a comprehensive assessment of the brain. In this study, we have mapped gray matter density by means of voxel-based morphometry on T1-weighted MRI volume sets in 19 patients with mild AD and 16 healthy subjects of similar age and gender ratio and report highly significant clusters of gray matter loss with almost symmetrical distribution, affecting mainly and in decreasing order of significance the medial temporal structures, the posterior cingulate gyrus and adjacent precuneus, and the temporoparietal association and perisylvian neocortex, with only little atrophy in the frontal lobe. The findings are discussed in light of previous studies of gray matter atrophy in AD based either on postmortem or neuroimaging data and in relation to PET studies of resting glucose consumption. The limitations of the method are also discussed in some detail, especially with respect to the segmentation and spatial normalization procedures as they apply to pathological brains. Some potential applications of voxel-based morphometry in the study of AD are also mentioned.

Aged↗
PubMed2006

Micro-blood-brain barrier openings and cytotoxic fragments of amyloid precursor protein accumulation in white matter after ischemic brain injury in long-lived rats.

Our study demonstrates that ischemia-reperfusion brain injury induces an increase in blood-brain barrier (BBB) permeability in the periventricular white matter. This chronic insufficiency of BBB may allow entry of neurotoxic fragments of amyloid precursor protein (APP) and other blood components such as platelets into the perineurovascular white matter tissue. These components may have secondary and chronic harmful effects on the ischemic myelin and axons and can intensify the phagocytic activity of microglial cells. Pathological accumulation of toxic fragments of APP in myelinated axons and oligodendrocytes appears after ischemic BBB injury and seem to be concomitant with, but independent of neuronal injury. It seems that ischemia-reperfusion disturbances may play important roles, both directly and indirectly, in the pathogenesis of white matter lesions. This pathology appears to have distribution similar to that of sporadic Alzheimer's disease. We noted micro-BBB openings in ischemic white matter lesions that probably would act as seeds of future Alzheimer's-type pathology.

Amyloid beta-Protein Precursor↗
PubMed1990

Accumulation of oedema fluid in deep white matter after cerebral cold injury.

The distribution of oedema fluid was examined in cats subjected to a cryogenic cortical injury. The lesion was made in the parietal cortex, and the animals were sacrificed 6 hr after the injury. The serum concentration of 125I bovine serum albumin was kept constant over the 6 hr period by a programmed infusion. Autoradiograms were made from the coronal sections through the lesion and were used to quantify densitometrically the regional content of extravasated serum albumin. After autoradiographic exposure, the section was stained with luxol-fast blue (LFB), and the degree of LFB discoloration was quantified. The maximal accumulation of extravasated serum albumin was observed in the deeper white matter under the subcortical white matter and not in the subcortical white matter of the lesion. The degree of oedema indicated by LFB discoloration showed a similar distribution pattern. This indicates that the compliance of the white matter in vasogenic oedema is regionally different. This difference of regional compliance seems to depend on the structural characteristics of each region such as the type of the fibers and the orientation of the fibers.

Animals↗
PubMed1991

Migration of xenogenic astrocytes in myelinated tracts: a novel probe for immune responses in white matter.

Experimental brain transplantation allows the study of the development of the immune response against brain antigens within the brain itself. This laboratory has developed a transplantation model in which rabbit embryo brain fragments are placed in the brains of newborn mice. The migration of xenogenic astrocytes is traced by a monoclonal antibody which combines with donor but not host glial fibrillary acidic protein. In the first 4 weeks after transplantation, the donor astrocytes successfully migrate, often within myelinated tracts. Following this period, T cells make their appearance and xenogenic astrocytes disappear by 10 weeks. The propensity for clearly identified foreign astrocytes to migrate in myelinated tracts coupled with a well-defined time course of host-vs-graft interaction suggested that the model could be used to study the immune response in white matter. The studies reported here provide sequential examples of the relationship between migration by foreign astrocytes in myelinated tracts and the development of the host immune response. Extensive migration in white matter tracts was first observed in the absence of any T cell response. Subsequently T cells were found at the transplantation site. Finally Ia was found to be expressed on blood vessels and microglia were strongly reactive in white matter that contained T cells but no foreign astrocytes. These observations support the suggestion that the model can be used to more precisely define cellular immune events that occur within white matter.

Animals↗
PubMed1989

The value of T1-weighted images in the differentiation between MS, white matter lesions, and subcortical arteriosclerotic encephalopathy (SAE).

The aim of the study was to define reliable criteria for the differentiation of MR imaging between patients with MS and with "vascular" white matter lesions/SAE. We examined 35 patients with proven MS according to the Poser criteria and 35 patients with other white matter lesions and/or SAE. The result is that with MR a differentiation can be achieved provided that T1-weighted spin-echo sequences are included and the different pattern of distribution is considered. MS plaques are predominantly located in the subependymal region, vascular white matter lesions are mainly located in the water-shed of the superficial middle cerebral branches and the deep perforating long medullary vessels in the centrum semiovale. Infratentorial lesions are more often seen in MS. Confluence at the lateral ventricles is frequently accompanied by confluent abnormalities around the third ventricle, Sylvian aqueduct, and fourth ventricle, which is uncommon in SAE. In MS many lesions visible on T2-weighted images have a cellular or intracellular composition that renders them visible also on T1-weighted ones as regions with low signal intensity and more or less distinct boundary. "Vascular" white matter lesions and SAE mainly represent demyelination and can therefore be seen on T2-weighted images, but corresponding low signal intensity lesions on T1-weighted images are uncommon. In some exceptions there are such lesions with low signal representing lacunar infarcts or widened Virchow-Robin-spaces.

Brain↗
PubMed1989

An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters.

An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters is reported. A 33-year-old woman showed a progressive dementia and died of cardiac failure at the age of 45. Neurological examination disclosed choreatic movements, myoclonus, rigidity, and generalized convulsion. Gross inspection of the brain showed a diffuse cerebral atrophy and marked degenerations of both the subcortical gray and white matters. Microscopically, numerous and extensive argyrophilic changes such as senile plaques, neurofibrillary tangles, and granulovacuolar degenerations were observed in the brain. The present case was characterized by a severe neuronal loss in the basal ganglia, substantia nigra, dentate nucleus, and thalamus as well as a marked myelin loss and axonal damage in the cerebral white matter. This case suggested a combination of multisystemic degeneration and primary degeneration of the cerebral white matter. The pathological similarity of this case to Creutzfeldt-Jakob disease and Pick's disease is discussed.

Adult↗
PubMed1980

Experimental transmission of human subacute spongiform encephalopathy to small rodents. II. Ultrastructural study of spongy state in the gray and white matter.

Light and electron microscopic findings of spongy state in four species of small rodents, viz, mice, rats, Mongolian gerbils, and guinea pigs, are described. The spongy state existed in both gray and white matter; its intensity varied in each species, and in the gray matter corresponded to vacuoles within the neuropil. They were of two types; one was the true vacuoles within neurites, and the other was markedly swollen cell processes, some of which were also identified as neurites. In the white matter, the spongy state corresponded mainly to distension of the myelin sheaths, due to splitting of the major dense line or swelling of the inner loop, and partly to intra-axonal vacuoles. In mice before appearance of clinical symptoms, the vacuolation occurred first in the cerebral white matter 5 weeks after inoculation and in the cerebral cortex at 7 weeks. The occurrence and development of the vacuoles are discussed.

Animals↗
PubMed1995

Bovine brain gray and white matter exhibit differential protein prenyl transferase activity.

Protein farnesyl transferase and geranylgeranyl transferase-I activities were determined in gray and white matter from various regions of bovine brain. Farnesyl transferase activity was 3-8 times greater than geranylgeranyl transferase-I activity. However, farnesyl transferase activity was about 2 times greater in the white matter than in the gray matter in all regions of the brain. Mixing experiments indicated lack of farnesyl transferase activators in white matter. This difference in farnesyl transferase activity may be due to enzyme content and may have implications in brain cell function.

Alkyl and Aryl Transferases↗
PubMed1988

Selective effect of mannitol-induced hyperosmolality on brain interstitial fluid and water content in white matter.

We studied the effect of mannitol-induced hyperosmolality on brain interstitial fluid (ISF) by autoradiography. Adult cats underwent intracerebral infusion of the extracellular marker, 14C-sucrose. Nine animals were given 2g/kg of mannitol intravenously, and another nine animals without mannitol were controls. Plasma and cerebrospinal fluid (CSF) osmolalities were measured. After 2 hr the brains were removed for determination of water and electrolyte content and for preparation of the autoradiograms. Diffusion coefficients were calculated for intracerebral transport with equations for radial diffusion. We found that mannitol increased the plasma osmolality but did not affect that of the CSF. Water and potassium contents were significantly lower in the white matter of mannitol-treated animals than in controls. Diffusion was reduced in the direction of gray matter into the white matter. We conclude that lower doses of mannitol control CSF pressure by selectively removing water from white matter, reducing the CSF volume, and affecting molecular transport at the gray/white interface.

Animals↗
PubMed1993

White matter abnormalities in patients with treated hyperphenylalaninaemia: magnetic resonance relaxometry and proton spectroscopy findings.

In order to further clarify the pathogenesis and clinical significance of MRI white matter abnormalities in treated hyperphenylalaninaemia (HPA), ten patients (seven type I HPA, two type II and one type III) underwent T2 relaxometry (n = 8) and/or 1H spectroscopy (n = 7) in addition to conventional MR spin-echo imaging at 1.5 T. Two patients with severe MRI abnormalities had repeat examinations during and after a 6- to 8-month period of strict diet control. The clinical evaluation included a detailed neurological examination. In nine out of ten patients visual evoked potentials (VEP) were obtained parallel to the MR examination. MR imaging demonstrated typical symmetrical areas of prolonged T2 relaxation time predominantly in the posterior periventricular white matter in all but one of type I and II patients. There was no consistent relationship between MRI findings and time of diagnosis/initiation of therapy, IQ or visual evoked potential changes. MRI abnormalities tended to be more severe in patients with poor dietary control and high current plasma phenylalanine levels, whereas a normal MRI was found only in patients with plasma phenylalanine levels continuously below 0.36 mmol/l. There was marked regression of MRI abnormalities already after 3 months of strict diet control. T2 relaxometry showed a bi-exponential behaviour of T2 in the affected white matter, with a slow component of about 200-450 ms, indicating an increase in free (extracellular) water. 1H spectroscopy revealed no signs of severe neuronal damage. We conclude, that the observed white matter changes in treated HPA probably represent reversible structural myelin changes rather than permanent demyelination.

Adolescent↗
PubMed1995

Creatine and nucleoside triphosphates in rat cerebral gray and white matter.

In vivo localized nuclear magnetic resonance spectroscopy has shown three-fold higher phosphocreatine/nucleoside triphosphate (PCr/NTP) ratios in cerebral white compared to gray matter. To interpret these results, total creatine (Cr) and ATP concentrations were measured enzymatically in samples taken from rapidly frozen rat cerebral cortex and corpus callosum. Total Cr (PCr plus Cr) and ATP concentrations were the same in the two regions. High performance liquid chromatography showed similar concentrations of total NTP in the two regions. These results suggest that higher in vivo PCr/NTP ratios in white compared to gray matter may be due to a higher PCr/Cr ratio in white matter and/or higher percentages of non-adenine mono- or diphosphate nucleotides in gray matter.

Animals↗
PubMed1993

Neuropathological and neurophysiological effects of interstitial white matter autologous and non-autologous protein containing solutions: further evidence for a glioma derived permeability factor.

The feline infusion model of brain edema was used to evaluate the pathophysiological effects of 0.6 ml infusions of autologous serum protein (66%), human serum protein (66%), human glioma cyst fluid and a tissue culture medium (TCM) on the structure and function of the forebrain white matter. These infusions increased local white matter water content by between 10.8 and 12.5 ml/100 g brain and were associated with moderate increases in ICP and CSF outflow resistance and a significant decrease in lumped craniospinal compliance. Cortical somatosensory potentials, motor evoked potentials, EEG and local cerebral blood flow (rCBF) at normocapnia were generally unchanged by the various infusions. All infusates except the 66% autologous serum protein infusion impaired rCBF CO2 reactivity. Histologically all infusates caused marked extracellular edema. The autologous serum protein infusion caused no additional histological changes whereas the glioma cyst infusates caused profound endothelial and astrocytic swelling, focal endothelial necrosis, basement membrane disruption, perivascular microglial reaction and pavementation and perivascular migration of polymorphonuclear leukocytes. Similar but less marked changes were seen after infusion of human serum protein whilst the TCM produced only minimal changes. The intensity and extent of Evans Blue extravasation into the forebrain white matter was greatest with glioma cyst infusates and with all infusions reflected the extent to microvascular changes. These studies show that products derived from gliomas cause additional damage to the blood-brain-barrier than that caused by non-autologous serum proteins. These results add further support for the existence of glioma derived permeability factors (GDPF), but suggest neither serum proteins nor glioma derived compounds in the white matter interstitium significantly influence local electrophysiological function. Some limitations of the infusion edema model when using non-autologous infusions and difficulties quantitating brain dysfunction are emphasised.

Animals↗
PubMed1996

Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts?

Forty-four patients (mean age 66, SD 8 years) with either clinical evidence of a focal lacunar syndrome (n = 36) or with disorders of memory or gait (n = 8) in the presence of a lacunar infarct on CT were studied for cognitive functioning and for the presence of white matter lesions on MRI. MR images were assessed by a neurologist and a neuroradiologist blinded to the clinical data. Thirty-six patients had one or more lacunar infarcts on CT or MRI (in the thalamus in 5, in the caudate nucleus in 3 and in the internal capsule or corona radiata in the remaining patients). Twelve patients had multiple infarcts. Severe lesions of the white matter were found in 13 patients, mild to moderate lesions in 20 patients. Scores on Digit Span, Digit Symbol and delayed recall of the 15-Words test were significantly lower in group with severe lesions, whilst there was a trend in the same direction for the Cognitive part of the Cambridge Examination of Mental Disorders in the Elderly, the Trailmaking B, Stroop colour interference test and the delayed visual reproduction of the Wechsler Memory Scale. These findings suggest that diffuse lesions of the white matter are an independent factor in the pathogenesis of intellectual dysfunction, also in patients with lacunar infarcts, but a truly independent analysis is difficult because the most severe involvement of the white matter tended to be associated with the largest number of lacunar infarcts.

Aged↗
PubMed1991

Lipid and fatty acid composition is altered in plaque tissue from multiple sclerosis brain compared with normal brain white matter.

Plaques and white matter from brains of multiple sclerosis (MS) patients were analyzed for lipid content, class composition, and fatty acid composition of total lipid, together with the fatty acid composition of plaque glycerophospholipids, and the results were compared with white matter from normal brain. Plaques contained less than 30% of the lipid present in normal white matter. Plaque lipid was characterized by significantly increased proportions of glycerophospholipids and decreased cerebrosides and sulfatides. In addition, a subacute plaque contained approximately 10 times the proportion of steryl esters observed in chronic plaques or normal white matter. Total lipid from all the MS plaques showed significantly increased percentages of saturated fatty acids, n-6, n-3 and total polyunsaturated fatty acids and decreased percentages of monoenes and alk-l-enyl ethers in comparison with normal brains. These results were consistent with increased cellularity and astrogliosis associated with MS plaques. However, analysis of plaque glycerophospholipids showed that the fatty acid changes observed in total lipid were not simply due to the increased proportion of glycerophospholipids and decreased myelin lipids, but that the fatty acid composition of the individual glycerophospholipids was different.

Brain↗
PubMed2002

The comparison study of compost and natural organic matter samples.

Sewage sludge is a serious problem facing modern wastewater treatment plants. One of the methods to safely utilize the sludge is through composting and the agricultural use of the final product. In this study the compost samples from municipal sewage sludge are compared to the natural, rich in organic matter samples. Based on physicochemical properties of the material, the maturity indices are obtained to evaluate the quality of organic matter and estimate the similarities between the samples. The study shows that one-dimensional analysis like that based on maturity indices does not provide satisfactory answers concerning the nature of such complex materials. The data set of the analysis naturally possesses a multidimensional character so that the employment of advanced chemometric techniques like cluster analysis show a number of features which were hidden within the 'data flood'. The major conclusion of this work is that the compost from sewage sludge is similar to peat in the significance of the properties of the organic matter. Moreover, the organic matter of agricultural soil, which is most stable and has been naturally matured over a long period of time, differs substantially from the other samples.

Agriculture↗
PubMed1997

On the crucial stages in the origin of animate matter.

Theories of the origin of life have proposed hypotheses to link inanimate to animate matter. The theory proposed here derived the crucial stages in the origin of animate matter directly from the basic properties of inanimate matter. It asked what were the general characteristics of the link, rather than what might have been its chemical details. Life and its origin are shown to be one continuous physicochemical process of replication, random variation, and natural selection. Since life exists here and now, animate properties must have been initiated in the past somewhere. According to the theory, life originated from an as yet unknown elementary autocatalyst which occurred spontaneously, then replicated autocatalytically. As it multiplied to macroscopic abundance, its replicas gradually exhausted their reactants. Random chemical drift initiated diversity among autocatalysts. Diversity led to competition. Competition and depletion of reactants slowed down the rates of net replication of the autocatalysts. Some reached negative rates and became extinct, while those which stayed positive "survived." Thus chemical natural selection appeared, the first step in the transition from inanimate to animate matter. It initiated the first animate property, fitness, i.e., the capacity to adapt to the environment and to survive. As the environment was depleted of reactants, it was enriched with sequels-namely, with decomposition products and all other products which accompany autocatalysis. The changing environment exerted a selective pressure on autocatalysts to replace dwindling reactants by accumulating sequels. Sequels that were incorporated into the autocatalytic process became internal components of complex autocatalytic systems. Primitive forms of metabolism and organization were thus initiated. They evolved further by the same mechanism to ever higher levels of complexity, such as homochirality (handedness) and membranal enclosure. Subsequent evolution by the same mechanism generated cellular metabolism, cell division, information carriers, and a genetic code. Theories of self-organization without natural selection are refuted.

Catalysis↗
PubMed2005

[White matter lesions as a risk factor for stroke and dementia. A population-based study in 85-year-olds].

AIM: This study was performed to determine whether white matter lesions on cranial computed tomography (cCT) are associated with increased prevalence and incidence of stroke, dementia, and mortality. METHODS: A representative sample of 239 85-year-olds living in Gothenburg, Sweden, was examined in a population-based study. Stroke was defined by information from patient reports, key informants, and an inpatient register system. Dementia was diagnosed according to DSM-III-R. White matter lesions (WML) and infarcts were determined by cCT. Follow-up examinations were performed 3 years later. RESULTS: White matter lesions doubled the odds of previous stroke (OR 1.8, 95% CI 1.03-3.3). Individuals with WML and stroke showed higher prevalence of dementia (OR 16.5, 95% CI 6.5-41.8) and mortality (OR 12.4, 95% CI 5.1-30.0) than those without WML and stroke. CONCLUSION: White matter lesions are common in the elderly, and these changes have clinical consequences increasing the risk of stroke. Whether preventive mechanisms could lead to risk reduction should be clarified in further studies.

Aged↗
PubMed2005

Prefrontal and temporal gray matter density decreases in opiate dependence.

RATIONALE: There have been only a few structural brain-imaging studies, with varied findings, of opiate-dependent subjects. Voxel-based morphometry (VBM) is suitable for studying whole brain-wise structural brain changes in opiate-dependent subjects. OBJECTIVES: The objective of the current study is to explore gray matter density in opiate-dependent subjects. METHODS: Gray matter density in 63 opiate-dependent subjects and 46 age- and sex-matched healthy comparison subjects was compared using VBM. RESULTS: Relative to healthy comparison subjects, opiate-dependent subjects exhibited decreased gray matter density in bilateral prefrontal cortex [Brodmann areas (BA) 8, 9, 10, 11, and 47], bilateral insula (BA 13), bilateral superior temporal cortex (BA 21 and 38), left fusiform cortex (BA 37), and right uncus (BA 28). CONCLUSIONS: This study reports that opiate-dependent subjects have gray matter density decreases in prefrontal and temporal cortex, which may be associated with behavioral and neuropsychological dysfunction in opiate-dependent subjects.

Adult↗