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PubMed2000

Role of L- and N-type calcium channels in the pathophysiology of traumatic spinal cord white matter injury.

Recent work has suggested a potential role for voltage-gated Ca(2+) channels in the pathophysiology of anoxic central nervous system white matter injury. To examine the relevance of these findings to neurotrauma, we conducted electrophysiological studies with inorganic Ca(2+) channels blockers and L- and N-subtype-specific calcium channel antagonists in an in vitro model of spinal cord injury. Confocal immunohistochemistry was used to examine for localization of L- and N-type calcium channels in spinal cord white matter tracts. A 30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber and injured with a modified clip (2g closing force) for 15s. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential at two points with glass microelectrodes. The compound action potential decreased to 71.4+/-2.0% of control (P<0. 05) after spinal cord injury. Removal of extracellular Ca(2+) promoted significantly greater recovery of compound action potential amplitude (86.3+/-7.6% of control; P< 0.05) after injury. Partial blockade of voltage-gated Ca(2+) channels with cobalt (20 microM) or cadmium (200 microM) conferred improvement in compound action potential amplitude. Application of the L-type Ca(2+) channel blockers diltiazem (50 microM) or verapamil (90 microM), and the N-type antagonist omega-conotoxin GVIA (1 microM), significantly enhanced the recovery of compound action potential amplitude postinjury. Co-application of the L-type antagonist diltiazem with the N-type blocker omega-conotoxin GVIA showed significantly greater (P<0.05) improvement in compound action potential amplitude than application of either drug alone. Confocal immunohistochemistry with double labelling for glial fibrillary acidic protein, GalC and NF200 demonstrated L- and N-type Ca(2+) channels on astrocytes and oligodendrocytes, but not axons, in spinal cord white matter. In conclusion, the injurious effects of Ca(2+) in traumatic central nervous system white matter injury appear to be partially mediated by voltage-gated Ca(2+) channels. The presence of L- and N-type Ca(2+) channels on periaxonal astrocytes and oligodendrocytes suggests a role for these cells in post-traumatic axonal conduction failure.

Animals↗
PubMed1999

Mechanisms of ischaemic damage to central white matter axons: a quantitative histological analysis using rat optic nerve.

The mechanism of ischaemic injury to white matter axons was studied by transiently depriving rat optic nerves in vitro of oxygen and glucose. Light and electron microscopic analysis showed that increasing periods of oxygen/glucose deprivation (up to 1 h) caused, after a 90-min recovery period, the appearance of increasing numbers of swollen axons whose ultrastructure indicated that they were irreversibly damaged. This conclusion was supported by experiments showing that the damage persisted after a longer recovery period (3 h). To quantify the axonal pathology, an automated morphometric method, based on measurement of the density of swollen axons, was developed. Omission of Ca2+ from the incubation solution during 1 h of oxygen/glucose deprivation (and for 15 min either side) completely prevented the axonopathy (assessed following 90 min recovery). Omission of Na+ was also effective, though less so (70% protection). The classical Na+ channel blocker, tetrodotoxin (1 microM), provided 92% protection. In view of this evidence implicating Na+ channels in the pathogenesis of the axonal damage, the effects of three different Na+ channel inhibitors, with known neuroprotective properties towards gray matter in in vivo models of cerebral ischaemia, were tested. The compounds used were lamotrigine and the structurally-related molecules, BW619C89 and BW1003C87. All three compounds protected the axons to varying degrees, the maximal efficacies (observed at 30 to 100 microM) being in the order: BW619C89 (>95% protection) > BW1003C87 (70%) > lamotrigine (50%). At a concentration affording near complete protection (100 microM), BW619C89 had no significant effect on the optic nerve compound action potential. Experiments in which BW619C89 was added at different times indicated that its effects were exerted during two distinct phases, one (accounting for about 50% protection) was during the early stage of oxygen/glucose deprivation itself and the other (also about 50%) during the first 15 min of recovery in normal incubation solution. The results are consistent with a pathophysiological mechanism in which Na+ entry through tetrodotoxin-sensitive Na+ channels contributes to Na+ loading of the axoplasm which then results in a lethal Ca2+ overload through reversed Na(+)-Ca2+ exchange. The identification of BW619C89 as a compound able to prevent oxygen/glucose deprivation-induced injury to white matter axons without affecting normal nerve function opens the way to testing the importance of this pathway in white matter injury in vivo.

Animals↗
PubMed2001

Maturation of white matter in the human brain: a review of magnetic resonance studies.

This review focuses on the maturation of brain white-matter, as revealed by magnetic resonance (MR) imaging carried out in healthy subjects. The review begins with a brief description of the nature of the MR signal and its possible biological underpinnings, and proceeds with a description of MR findings obtained in newborns, infants, children and adolescents. On MR images, a significant decrease in water content leads to a decrease of longitudinal relaxation times (T1) and transverse relaxation times (T2) and consequent "adult-like" appearance of T1-weighted and T2-weighted images becomes evident towards the end of the first year of life. Owing to the onset of myelination and the related increase of lipid content, MR images gradually acquire an exquisite grey-white matter contrast in a temporal sequence reflecting the time course of myelination. Albeit less pronounced, age-related changes in white matter continue during childhood and adolescence; white matter increases its overall volume and becomes more myelinated in a region-specific fashion. Detection of more subtle changes during this "late" phase of brain development is greatly aided by computational analyses of MR images. The review also briefly outlines future directions, including the use of novel MR techniques such as diffusion tensor imaging and magnetization transfer, as well as the suggestion for the concurrent use of experimental behavioral test-batteries, with structural MR imaging, to study developmental changes in structure-function relationships.

Adolescent↗
PubMed1988

Congenital muscular dystrophy (Fukuyama type)--changes in the white matter low density on CT.

Sixty-two computed tomographic (CT) scans of 36 patients with congenital muscular dystrophy of Fukuyama type (FCMD) were analysed. A low density area in the cerebral white matter was characteristic of FCMD and a special reference was made to the changes in the white matter low density. It was present in 15 patients out of 36 (42%) and frequently seen in the scans obtained on the younger patients; among 11 scans taken of patients between 1 and 2 years of age, 10 scans (91%) showed the white matter low density. Repeated CT scans were carried out on 26 of the 36 cases. Follow-up study revealed that the white matter low density areas were most apparent around the age of one year and decreased or disappeared at 2 or 3 years of age. From these observations, delayed myelination was suspected for the pathogenesis of the low density area found in FCMD.

Adolescent↗
PubMed2003

Proton MR spectroscopy features of normal appearing white matter in neurofibromatosis type 1.

To determine whether differences exist between neurofibromatosis type 1 (NF1) patients with or without focal lesions and healthy normal volunteers in the metabolite ratios of normal appearing white matter, 27 patients with NF1 (with parenchymal lesion, MR positive, n: 17; without parenchymal lesions, MR negative, n: 10) and 20 healthy volunteers underwent MRI and short TE (31 ms) proton MR spectroscopy (MRS). In 17 patients with parenchymal lesions, 61 focal lesions were detected by MRI. MRS was performed from normal appearing frontal and posterior parietal white matter (FWM and PWM) in NF1 and from control groups. NAA/Cr, Cho/Cr and MI/Cr ratios were calculated. Significant increase in Cho/Cr and MI/Cr ratios were found in FWM and PWM in MR negative and positive groups when compared to control group. NAA/Cr ratio in MR positive group was significantly decreased in FWM compared to control group. There were no significant differences between FWM and PWM in all metabolite ratios of MR negative group. MI/Cr ratio in MR positive group was significantly elevated in PWM compared to FWM. Metabolite changes detected by MRS could indicate demyelination and gliosis in normal appearing white matter in all NF1 patients, and additionally neuroaxonal damage in the FWM of NF1 patients with focal lesions. For that reason, in the clinical evaluation and follow-up of these patients MRS features of normal appearing white matter should be considered in addition to focal lesions.

Adolescent↗
PubMed2003

A possible purification method of DNAs' fragments from humic matters in soil extracts using novel stimulus responsive polymer adsorbent.

Novel stimulus responsive, uniformly sized polymer-based adsorbent was prepared for a possible purification method of DNAs from humic matters in soil extracts. The prepared polymer adsorbent has a pair of anion exchangeable and cation exchangeable polymeric selectors, which are reversibly responded by the changes of column temperature as well as pH of mobile phase. At pH 5, DNAs and humic matters were completely adsorbed on the polymer adsorbent at room temperature, while up to 90% of the adsorbed DNAs were released and recovered at 70 degrees C with no release of adsorbed humic matters. Cleaning up of the polymer adsorbent could be performed by washing the adsorbed humic matters with alkaline mobile phase (pH 9) to recover those and realize repeatable use of the adsorbent.

Adsorption↗
PubMedDate not supplied

Incidence of lens matter dislocation during phacoemulsification.

PURPOSE: To assess the incidence and visual morbidity of lens matter dislocation during phacoemulsification and the relationship between this complication and surgical experience. SETTING: Teaching and district general hospitals. METHODS: A multiple-choice questionnaire was sent to members of the Northern and Midlands Ophthalmological Societies. They were asked about the incidence of lens matter dislocation, the visual outcome of the cases, and their surgical experience. RESULTS: Forty-seven of the 177 survey respondents (26.5%) were using phacoemulsification. The incidence of lens matter dislocation was 1.1%; 49.0% of the surgeons had experienced at least one case. The incidence increased significantly when surgeons assessed their expertise with phacoemulsification toward the expert end of the scale. Final visual acuity was worse than 6/12 in 35.0% of cases. CONCLUSIONS: The incidence of lens matter dislocation with phacoemulsification is significant and related to an incorrect assessment of expertise by the surgeons. The considerable visual morbidity associated with this complication can be minimized using the management strategy discussed.

Clinical Competence↗
PubMed1996

Multifocal white matter lesions.

There is a long differential diagnosis for multifocal white matter lesions on MR. The most common causes are prominent Virchow-Robin spaces, white matter ischemic change, and multiple sclerosis, but many other causes have been reported. Most of these are related to vascular or other demyelinating etiologies, but infectious/inflammatory disease, trauma, and neoplastic and other unusual causes may also be responsible. Typical imaging features of the more common multifocal white matter disorders are outlined, and the rarer causes are discussed briefly. An approach to imaging differential diagnosis is given, with emphasis on the differences between white matter ischemic lesions and multiple sclerosis.

Brain Diseases↗
PubMed2001

Update on genetic disorders affecting white matter.

The classification of diseases affecting white matter has changed dramatically with the use of magnetic resonance imaging. Classical leukodystrophies, such as metachromatic leukodystrophy and Krabbe's disease, account for only a small number of inherited diseases that affect white matter. Magnetic resonance imaging has clarified genetic disorders that result in white matter changes or leukoencephalopathies. The term leukoencephalopathy is used to reflect the broader number of diseases that may cause as either primary or secondary changes in myelin development. This review attempts to categorize white matter disorders into classes such as lipid, myelin protein, organic acids, and defects in energy metabolism, in addition to other causes.

Brain↗
PubMed1999

MRI signal changes in the white matter after corpus callosotomy.

Magnetic resonance imaging (MRI) changes reported after corpus callosotomy include hyperintensity in the corpus callosum, perifalcine hyperintensity caused by surgical retraction, and acute changes associated with surgical complications. The authors have observed MRI signal changes in the cerebral white matter of corpus callosotomy patients that are separate from the sectioned callosum and not clearly related to surgical manipulation or injury. Brain MRI scans were retrospectively reviewed in 25 of 38 patients who underwent anterior, posterior, or total callosotomy for refractory seizures between 1988 and 1995. Nine patients had signal changes in the cerebral white matter on postoperative MRI. Six of these patients had preoperative MRI studies available for comparison, and none of the white matter signal abnormalities were evident preoperatively. T2 prolongation or hyperintensity on proton-density images was observed in areas including the centrum semiovale, forceps major, and forceps minor. Three patients had signal changes that had distinct borders extending only to the posterior limit of the callosotomy. MRI signal changes in the cerebral white matter after corpus callosotomy have not been previously reported and may represent distant effects of callosal section. Wallerian degeneration occurring in the neuronal processes cut during surgery could account for the signal changes.

Adolescent↗
PubMed2001

Quinoid redox cycling as a mechanism for sustained free radical generation by inhaled airborne particulate matter.

The health effects of airborne fine particles are the subject of government regulation and scientific debate. The aerodynamics of airborne particulate matter, the deposition patterns in the human lung, and the available experimental and epidemiological data on health effects lead us to focus on airborne particulate matter with an aerodynamic mean diameter less than 2.5 microm (PM(2.5)) as the fraction of the particles with the largest impact in health. In this article we present a novel hypothesis to explain the continuous production of reactive oxygen species produced by PM(2.5) when it is deposited in the lung. We find PM(2.5) contains abundant persistent free radicals, typically 10(16) to 10(17) unpaired spins/gram, and that these radicals are stable for several months. These radicals are consistent with the stability and electron paramagnetic resonance spectral characteristics of semiquinone radicals. Catalytic redox cycling by semiquinone radicals is well documented in the literature and we had studied in detail its role on the health effects of cigarette smoke particulate matter. We believe that we have for the first time shown that the same, or similar radicals, are not confined to cigarette smoke particulate matter but are also present in PM(2.5). We hypothesize that these semiquinone radicals undergo redox cycling, thereby reducing oxygen and generating reactive oxygen species while consuming tissue-reducing equivalents, such as NAD(P)H and ascorbate. These reactive oxygen species generated by particles cause oxidative stress at sites of deposition and produce deleterious effects observed in the lung.

Air Pollutants↗
PubMed1996

GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination.

To investigate the structural role of glial fibrillary acidic protein (GFAP) in vivo, mice carrying a null mutation in GFAP were generated. In 7/14 mutant animals older than 18 months of age, hydrocephalus associated with white matter loss was detected. Mutant mice displayed abnormal myelination including the presence of actively myelinating oligodendrocytes in adults, nonmyelinated axons in optic nerve, and reduced myelin thickness in spinal cord. White matter was poorly vascularized and the blood-brain barrier was structurally and functionally impaired. Astrocytic structure and function were abnormal, consisting of shortened astrocytic cell processes, decreased septation of white matter, and increased CNS extracellular space. Thus, GFAP expression is essential for normal white matter architecture and blood-brain barrier integrity, and its absence leads to late-onset CNS dysmyelination.

Aging↗
PubMed2000

Microstructure of temporo-parietal white matter as a basis for reading ability: evidence from diffusion tensor magnetic resonance imaging.

Diffusion tensor magnetic resonance imaging (MRI) was used to study the microstructural integrity of white matter in adults with poor or normal reading ability. Subjects with reading difficulty exhibited decreased diffusion anisotropy bilaterally in temporoparietal white matter. Axons in these regions were predominantly anterior-posterior in direction. No differences in T1-weighted MRI signal were found between poor readers and control subjects, demonstrating specificity of the group difference to the microstructural characteristics measured by diffusion tensor imaging (DTI). White matter diffusion anisotropy in the temporo-parietal region of the left hemisphere was significantly correlated with reading scores within the reading-impaired adults and within the control group. The anisotropy reflects microstructure of white matter tracts, which may contribute to reading ability by determining the strength of communication between cortical areas involved in visual, auditory, and language processing.

Adult↗
PubMed2000

Dry matter intake, apparent digestibility and excretion of purine derivatives in sheep fed tropical legume hay.

Four ruminally cannulated wethers (31+/-1.3kg) were used in an experiment with a 4x4 Latin square design to estimate the DM intake, apparent digestibility, nitrogen balance, rumen ammonia and microbial protein production. The sheep had ad libitum access to either Cassia rotundifolia (Cassia), Lablab purpureus (Lablab), Macroptilium atropurpureum (Siratro) or Stylosanthes guianensis (Stylo). Dry matter intake of cassia was lower (P<0.001) than that of lablab, siratro and stylo hays. Organic matter intake was greater (P<0.001) for lablab, siratro and stylo hays than that of cassia. Dry matter digestibility was higher (P<0.05) for lablab hay, than that of cassia, siratro and stylo hays. The organic matter digestibility ranged from 0.579 for cassia hay to 0.617 for stylo hay and there were no differences (P0.05) among the legume hays. Nitrogen intake was highest (P<0.05) in sheep given stylo hay and least in sheep fed cassia hay. Animals given lablab, siratro and stylo hays had higher (P<0.05) faecal and urinary N compared to those on cassia hay. Rumen ammonia N concentration was highest (P<0.05) in sheep given lablab while sheep offered siratro and stylo had intermediate values, and least in animals fed cassia hay. The ammonia levels were above the recommended optimal level of 50mg N/l. The total purine derivative excretion in the urine and microbial N supply was not different (P0.05) among treatments. From the presented findings it is concluded that the intake and digestibility in sheep of the four legume hays are variable and provide adequate rumen ammonia N for maximum rumen microbial growth making then ideal protein supplements to ruminants fed low quality roughages.

Journal Article↗
PubMed2002

Development of a semi-automated method for quantification of MRI gray and white matter lesions in geriatric subjects.

Brain magnetic resonance imaging (MRI) allows for quantitative assessment of hyperintense foci, which are seen with aging and various diseases. These foci, considered to represent lesions, are important in the study of various psychiatric illnesses, including depression. Few quantitative measures have been developed for such research. The goal of the current study was to develop a reliable and efficient method for quantifying the volumes of gray and white matter lesions in MRI scans of the elderly. Interrater reliability was determined by repeat lesion measures on 16 scans. Semi-automated segmentation was performed that identified potential lesions, and then lesions were manually selected based upon detailed anatomic criteria. The lesion quantification procedure took between 25 and 45 min per scan. Reliability intraclass correlation coefficients (ICCs) were 0.99 for both gray and white matter lesions. Volumetric results were found to be moderately correlated with previous lesion ratings (r-values between 0.37 and 0.62, P<0.0001). Among the 700 scans processed with this method, lesion volumes ranged from 0 to 7.3 ml for gray matter, and from 0.4 to 96.8 ml for white matter. Our method proved to be efficient and reliable for quantifying lesions in MRI scans of the elderly.

Aged↗
PubMed2003

Sex-dependent effects of schizophrenia: an MRI study of gyral folding, and cortical and white matter volume.

Alterations, sometimes sex-dependent, in volumes and gyral structure of areas of cerebral cortex have been reported in schizophrenia. Such changes imply an anomaly of connectivity. The gyrification, percentage of tissue volume attributed to white matter, cortical volume and white matter volume were measured from magnetic resonance images in males and females with (n = 61) and without (n = 42) schizophrenia. The frontal, temporal and an amalgam of occipital and parietal lobes were examined in both hemispheres. There was no effect of schizophrenia on the gyrification of the brain. For the volume of occipito-parietal white matter, females with schizophrenia had bilaterally lower volumes, while males with schizophrenia had greater volumes than controls. It is concluded that the changes in connectivity underlying the pathogenesis of schizophrenia are sex-specific and expressed in occipito-parietal white matter.

Adult↗
PubMed2001

Early white matter changes on brain magnetic resonance imaging in a newborn affected by merosin-deficient congenital muscular dystrophy.

In 1996 we reported sequential magnetic resonance imaging study in an infant with merosin-deficient congenital muscular dystrophy with normal brain magnetic resonance imaging at 3 weeks and white matter changes by 6 months. We now report an infant with merosin-deficient congenital muscular dystrophy with a mild degree of white matter changes already present on brain magnetic resonance imaging at 5 days of age. The difference may be due to a difference in the T2 sequences used. The images in this present case were obtained with a fast spin echo sequence (echo time: 210 ms). The increased T2 weighted may be responsible for a better detection of the white matter changes at an early stage, when they can be missed on conventional, less weighting T2 sequences. These results suggest that, by using appropriate sequences, mild white matter changes may be detectable on brain magnetic resonance imaging in the first days of life in infants with merosin-deficient congenital muscular dystrophy.

Age of Onset↗
PubMed2003

Optimization of TI values in inversion-recovery MR sequences for the depiction of fine structures within gray and white matter: separation of globus pallidus interna and externa.

RATIONALE AND OBJECTIVES: The authors' purpose was to search the inversion time (TI) values that enable the best differentiation of fine structures in gray matter (gray-gray differentiation). MATERIALS AND METHODS: Seven healthy adult volunteers with no history of neurologic disease or head trauma were recruited and gave their informed consent. The subjects consisted of two men and five women ranging in age from 25 to 38 years, with a mean age of 28 years +/- 5. The subjects were imaged with a turbo spin-echo inversion-recovery sequence. This sequence was performed in the axial plane at the level of the basal ganglia with the following parameters: repetition time, 3,200 msec; echo time, 15 msec; three signals acquired; echo train, seven; section thickness, 3 mm; matrix size, 256 x 256; and field of view, 180 mm. The tested values were TI = 100, 200, 300, 400, and 500 msec. Region-of interest measurements were performed at the following anatomic structures and represent gray-gray and white-white differentiations, respectively: globus pallidus externa versus globus pallidus interna, and optic radiation versus surrounding white matter. RESULTS: The maximum contrast index value occurred at TI = 400 msec for globus pallidus externa versus globus pallidus interna (P < .05) With the contrast-to-noise ratio, no significant difference in gray-gray differentiation was observed among the various TIs. The minimum signal-to-noise ratio of the gray matter occurred at TI = 400 msec (P < .05). A subjective evaluation revealed an overall superiority of gray-matter differentiation with TI = 400 msec. CONCLUSION: A TI of 400 msec was the most suitable for this purpose.

Adult↗