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PubMed1987

Radiation effects on cerebral white matter: MR evaluation.

The purpose of this study was to evaluate the white-matter changes associated with cranial radiation by MR imaging. The MR scans of 95 patients receiving conventional external beam radiation for a wide variety of central nervous system tumors were reviewed. Moderately T2-weighted spin-echo images with a 2000-msec repetition time and 56-msec-echo time were analyzed for white-matter abnormalities without knowledge of the patient's history. These were correlated with radiation dose, port, and time interval since completion of therapy, and then compared with an age-matched control group of 180 patients with nonirradiated, space-occupying, intracranial lesions. Radiation-related lesions were characterized as symmetric, high-signal foci in the periventricular white matter. Relative sparing of the posterior fossa, basal ganglia, and internal capsules was noted. In patients older than 20 years, these changes paralleled those seen in ischemia but were more prevalent (p less than .005). In 25 patients with sequential MR scans, these findings remained stable. In those patients with limited treatment fields, for example, pituitary adenomas, no statistical differences were seen between radiation-treated and nontreated groups. Cerebral white-matter changes that mimic deep white-matter infarction are frequently seen in response to therapeutic radiation. There is a variable incidence of radiation effects, becoming more marked in older patients. MR interpretation must consider the neuropathologic consequences of therapeutic radiation, which include demyelination, microvascular occlusion, and blood-brain barrier breakdown.

Adult↗
PubMed1994

MR detection of white matter disease of the brain in patients with HIV infection: fast spin-echo vs conventional spin-echo pulse sequences.

OBJECTIVE: Although fast spin-echo images and slower spin-echo images have similar contrast characteristics, the two techniques have not yet been shown to be equivalent in all aspects of brain imaging. To determine if the two sequences are equivalent, we compared detection of white matter lesions, image quality, and artifact degradation on fast spin-echo and spin-echo proton density-weighted and T2-weighted MR images of the brain in prospectively selected patients who were seropositive for HIV. SUBJECTS AND METHODS: Fast spin-echo and spin-echo MR images of the brain were obtained in 153 consecutive subjects. The images were reviewed independently by three experienced neuroradiologists. The size, number, and location of white matter lesions were compared for the two techniques. Image quality, motion artifact, CSF flow artifact, and gray-white matter differentiation were graded on a five-point scale. RESULTS: No statistical difference was found in gray-white matter differentiation. Overall image quality, CSF flow artifacts, and motion artifacts were slightly worse on the fast spin-echo images (p < .05). Although some variability existed in the detection of lesions less than 5 mm in diameter, the differences was small, and all larger lesions were detected by both techniques. Agreement between fast spin-echo and conventional spin-echo techniques was nearly exact with respect to characterizing findings in brain as either normal or abnormal. CONCLUSIONS: Fast spin-echo and spin-echo MR of the brain produce images of similar quality and show white matter lesions equally well. These results support the replacement of slower, conventional spin-echo pulse sequences with faster fast spin-echo sequences.

AIDS Dementia Complex↗
PubMed2000

The effect of aging on the apparent diffusion coefficient of normal-appearing white matter.

OBJECTIVE: The purpose of our study was to test the hypothesis that the apparent diffusion coefficient (ADC) of normal-appearing white matter increases with advancing age. SUBJECTS AND METHODS: We selected 38 patients with normal MR imaging findings from 332 patients undergoing clinical MR imaging. Diffusion-weighted MR imaging was performed with diffusion gradients applied in three orthogonal directions. For each patient, the average ADC on trace-weighted diffusion images of white matter at prespecified regions of interest and at the thalamus were compared with the patient's age. RESULTS: For the white matter, ADC sorted by patient age in decades increased with advancing age. Patients at least 60 years old had significantly higher ADC (0.769 +/- 0.019 mm(2)/sec x 10(-3)) than patients less than 60 years old (0.740 +/- 0.013 mm(2)/sec x 10(-3)) (p < 0.001). Comparison of individual white matter ADC and age showed a significant increase with advancing age (p < 0.0001). For the thalamus, the average ADC among patients at least 60 years old (0.766 +/- 0.015 mm(2)/sec x 10(-3)) exceeded the average ADC for patients less than 60 years old (0.745 +/- 0.022 mm(2)/sec x 10(-3)) (p < 0.05). However, comparison of individual thalamic ADC and patient ages, although showing a trend to higher ADC with increasing age, did not reach statistical significance (p = 0.06). CONCLUSION: Advancing age is associated with a small but statistically significant increase of water diffusibility in human white matter. A similar trend was present in the thalamus. These increases may reflect mild structural changes associated with normal aging.

Adult↗
PubMed1985

Influence of dietary alfalfa:orchardgrass hay and lasalocid on in vitro estimates of dry matter digestibility and volatile fatty acid concentrations of cecal contents and rate of digesta passage in sows.

Four mature crossbred sows were fistulated in the cecum, with two sows fed a corn-alfalfa:orchardgrass hay (46%) diet (CH) and two fed a corn-soybean meal diet (CS). Four experiments were conducted to evaluate buffers, incubation times, buffer pH and substrate and inocula sources in an in vitro, anaerobic, mixed-culture system. In vitro dry matter digestibility (IVDMD) and substrate solubility in buffer (SS) were determined. In Exp. 1, substrates were CH and CS diets with cecal inocula obtained from CH- and CS-fed sows. The bicarbonate (B) buffer resulted in lower (P less than .01) and less variable SS for all treatments. In vitro dry matter digestibility was higher (P less than .01) for the CS diet at both 24 and 48 h incubation. Use of the B buffer also resulted in higher (P less than .001) IVDMD values. In Exp. 2, substrates were either as in Exp. 1 or were freeze-dried cecal contents (CC) from CH- or CS-fed sows. In vitro dry matter digestibility of CC was lower (P less than .006) than IVDMD of diet, while IVDMD was higher (P less than .02) with cecal inocula than fecal inocula. In Exp. 3, substrate-inocula treatments were CH-CH, CH-CS, CS-CH and CS-CS. Substrate solubility was lower (P less than .05) at pH 5.8 than at pH 6.8. In vitro dry matter digestibility was higher when substrate and inocula were from the same source and at pH 5.8. In Exp. 4, CC and inocula were from sows fed CH and CS diets with or without lasalocid. In vitro dry matter digestibility was higher with CC from lasalocid-fed sows and inocula from sows fed no lasalocid. The CH diet resulted in higher acetate (Ac) and lower propionate (Pr) molar proportions than did the CS diet, while lasalocid increased molar proportion Pr and decreased molar proportion Ac in cecal contents from sows fed either diet. Corn-alfalfa:orchardgrass hay-fed sows had a faster rate of digesta passage and shorter cecal retention time than did CS-fed sows.

Animals↗
PubMed1989

[Age-related cerebral white matter changes on computed tomography].

Changes of cerebral white matter on computed cranial tomography related to aging were studied in 70 subjects aged 30 to 94 years. The subjects had no histories of cerebrovascular accidents and no abnormalities in the central nervous system were shown by physical examinations nd CT scans. We measured the average attenuation values (CT numbers) of each elliptical region (165 pixels, 0.39 cm2) in the bilateral thalamus and twelve areas of deep white matter. Multiple regression analysis was used to assess the effects of age, cranial size and cranial bone CT numbers on the brain CT numbers. We also studied the association between brain CT numbers and brain atrophy, hypertension, diabetes mellitus. CT numbers of frontal white matter surrounding anterior horns decreased with aging in 70 subjects aged 30 to 94 years. No significant correlation between age and brain CT numbers was found in any other region by multivariate analysis, because of the prominent effect of cranial bone CT numbers on brain CT numbers. Although no age-related changes of white matter CT numbers was found in 41 subjects aged 30 to 65 years, there were significant negative correlations between age and white matter CT numbers at all regions in 29 subjects aged 66 to 94 years. Brain atrophy was associated with brain CT numbers. No association was found for hypertension or diabetes mellitus. Brain CT numbers decreased with aging even in neurologically healthy persons in older age. Brain CT numbers also decreased as cerebral atrophy advanced.

Adult↗
PubMed2004

[A neuroradiological study on the influence of cerebral atrophy and white matter lesion on cognitive function in the elderly].

We investigated the influence of brain atrophy and white matter lesions on cognitive function in elderly people. We selected 33 subjects (mean age, 79.2 +/- 5.1yrs) with a MMSE score from 14 to 30 who had no previous history of stroke from the outpatients in the Memory Clinic of our hospital. These subjects were divided into four groups on the basis of their MMSE score as follows: 14-20; moderate dementia (Moderate-D, n = 9), 21-23; mild dementia (Mild-D, n = 9), 24-27; mild cognitive impairment (MCI, n = 10), 28-30; normal (Normal, n = 5). Among these four groups, we compared the frequency of the associated risk factors for cerebral infarction (hypertension, diabetes mellitus, hyperlipidemia, heart disease), and the severity of brain atrophy and cerebral white matter lesion which were visually evaluated by MRI technique. Brain atrophy and white matter lesions were assessed by reviewing the cerebral cortex and hippocampus, and deep white matter lesion (DWML) and periventricular hyperintensity (PVH), respectively. Brain atrophy was divided into three grades (mild, moderate, severe) and white matter lesions were classified into four grades (0-3) using Fazekas's criteria. We performed statistical analysis to detect t parameters which correlate with and influence MMSE scores from among the MRI findings. The cases with dementia were all diagnosed as Alzheimer's disease. There were no significant differences among the four groups in mean age, the incidence of individual associated risk factors, the severity of cortical atrophy, or the grade of DWML (< or = 2) and PVH (< or = 2). However, the frequency of hippocampal atrophic change greater than a moderate grade increased in parallel with the exacerbation of reduced cognitive function (Normal; 20%, MCI: 40%, Mild-D; 56%, Moderate-D 89%), and approximately 76% with such a change were AD cases. Statistical analysis showed a significant negative correlation between the grade of hippocampal atrophy and MMSE score (r = -0.518, p < 0.005) and a great influence of hippocampal atrophy on that score (step-wise regression analysis: r = 0.518, p < 0.005). From the above results, it was suggested that more than moderate atrophic change in the hippocampus might possibly be related with cognitive impairment and that both DWML and PVH less than the second grade had little influence on the decline of brain function.

Aged↗
PubMed1975

Influence of dry matter and nitrogen intakes on fecal nitrogen losses in cattle.

Dietary factors influencing loss of fecal nitrogen in Holstein steers have been examined in data on metabolism from forage diets. Two factors- total nitrogen and dry matter intake, accounted for a large part of the variation in fecal nitrogen. Nitrogen intak expressed as grams per kilogram dry matter intake more accurately accounted for variability in total fecal nitrogen than did nitrogen intake expressed as grams per animal per day. Data were from trials on 68 forages covering a range of nitrogen intakes and of nitrogen concentration in dry matter of forage. Correlations were .93 between total fecal nitrogen and dry matter intake, .90 between total fecal nitrogen and total nitrogen intake, and .95 between total fecal nitrogen and total fecal dry matter. However, at high and low nitrogen intake there was evidence of departure from a linear relationship. The relative usefulness of three regression analyses to estimate metabolic fecal nitrogen is discussed.

Animal Feed↗
PubMed2003

Delineating gray and white matter involvement in brain lesions: three-dimensional alignment of functional magnetic resonance and diffusion-tensor imaging.

OBJECT: The role of functional magnetic resonance (fMR) imaging has become increasingly important in the presurgical mapping of gray matter. Neurosurgical interventions often involve fiber bundles that connect critical functional areas. Recently, diffusion-tensor (DT) imaging has enabled the visualization of fiber bundle direction and integrity, thus providing the ability to delineate clearly white matter from gray matter tissue. The main objective of this study was to improve the presurgical assessment of critical functionality in the vicinity of brain lesions by combining DT and fMR imaging methodologies. METHODS: Twenty patients with various space-occupying brain lesions underwent imaging for presurgical evaluation of motor and/or somatosensory functions. The authors focus on five patients with diverse space-occupying brain lesions. Diffusion tensor-based fiber tracking and fMR imaging activation maps were superimposed in three dimensions to visualize pyramidal tracts corresponding to motor and somatosensory regional activation. CONCLUSIONS: The combination of DT and fMR imaging for presurgical functional brain mapping provides valuable information that cannot be extracted using either method alone. The validity and sensitivity of noninvasive functional mapping for surgical guidance could be improved by considering results obtained with both methods. Furthermore, the use of three-dimensional visualization seems crucial and unique for viewing and understanding the complicated spatial relationship among the lesion, gray matter activation, and white matter fiber bundles.

Adolescent↗
PubMed2005

Acute lipopolysaccharide-mediated injury in neonatal white matter glia: role of TNF-alpha, IL-1beta, and calcium.

Bacterial infection is implicated in the selective CNS white matter injury associated with cerebral palsy, a common birth disorder. Exposure to the bacterial endotoxin LPS produced death of white matter glial cells in isolated neonatal rat optic nerve (RON) (a model white matter tract), over a 180-min time course. A delayed intracellular Ca(2+) concentration ([Ca(2+)](i)) rise preceded cell death and both events were prevented by removing extracellular Ca(2+). The cytokines TNF-alpha or IL-1beta, but not IL-6, mimicked the cytotoxic effect of LPS, whereas blocking either TNF-alpha with a neutralizing Ab or IL-1 with recombinant antagonist prevented LPS cytotoxicity. Ultrastructural examination showed wide-scale oligodendroglial cell death in LPS-treated rat optic nerves, with preservation of astrocytes and axons. Fluorescently conjugated LPS revealed LPS binding on microglia and astrocytes in neonatal white and gray matter. Astrocyte binding predominated, and was particularly intense around blood vessels. LPS can therefore bind directly to developing white matter astrocytes and microglia to evoke rapid cell death in neighboring oligodendroglia via a calcium- and cytokine-mediated pathway. In addition to direct toxicity, LPS increased the degree of acute cell death evoked by ischemia in a calcium-dependent manner.

Animals↗
PubMed2005

Antidepressant exposure may protect against decrement in frontal gray matter volumes in geriatric depression.

OBJECTIVES: Depressed elderly patients with and without antidepressant exposure were compared to normal controls to examine the effects of prior antidepressant exposure on regional brain gray matter volumes using magnetic resonance imaging (MRI). METHOD: The study was conducted from October 1999 to January 2003. Patients and controls were closely matched by age and education. They underwent comprehensive neuropsychiatric and physical examinations. Measures of the total frontal lobe and the frontal gray and white matter volumes corrected by the intracranial volume were obtained using MRI, together with clinical measures of medical burden. Historical information about prior exposure to antidepressant drugs was collected using multiple information sources. The groups were compared using multivariate analyses of covariance, controlling for age, sex, and medical burden. RESULTS: The study sample comprised 41 patients who met the DSM-IV criteria for major depressive disorder (32 women; 11 antidepressant exposure and 30 drug-naive; mean age 70.5 years) and 41 controls (20 women; mean age 72.2 years). In the multivariate analysis, the depressed group had smaller corrected orbitofrontal cortex (OFC) total and gray matter volumes compared to the controls (p < .01). However, depressed patients with prior antidepressant exposure had larger OFC gray matter volumes compared to drug-naive depressed patients, but smaller than those in normal controls (p = .005). This effect was not explained by the group differences in sex ratio, age at onset of depression, or the number or duration of depressive episodes. CONCLUSIONS: We observed larger OFC regional volumes in depressed patients exposed to antidepressants compared to the drug-naive depressed subjects, but smaller than those in age-matched controls. Antidepressant exposure may protect against gray matter loss in geriatric depression.

Age Factors↗
PubMed1999

[Steroid-responsive diffuse cerebral white matter lesions in a case of intractable fungal meningoencephalitis].

We report a case of fungal meningoencephalitis with steroid-responsive diffuse cerebral white matter lesions. A 49-year-old male developed auditory hallucination, confusion and fever, on April, 1994. He was diagnosed as having cryptococcal meningoencephalitis based on the detection of cryptococcal antigens in the cerebrospinal fluid (CSF). Intravenous administration of fluconazole resulted in improvement of his neurologic symptoms and CSF findings. For the next seven months, he was treated with oral fluconazole and the neurological status was stable. However, soon after the dose of fluconazole was tapered, he became confused and febrile, which made him admitted to our hospital. Neurological examination on admission showed disturbance of consciousness, disorientation and meningeal irritation. The CSF examination revealed mild pleocytosis (mostly lymphocytes), elevated protein and normal glucose levels, although fungus was not detected. The T2-weighted image of brain MRI demonstrated diffuse hyperintense lesions in the bilateral cerebral white matters. GD-DTPA enhanced MRI showed spotty enhanced lesions in the periventricular white matters. The neurologic symptoms were once relieved after intravenous administration of fluconazole was started, but two months later, he became comatose and needed ventilatory support, despite amphotericine B therapy. Then, a needle brain biopsy targeting the white matter lesion was done. Histopathology of the specimen showed chronic inflammation with granuloma formation and T lymphycyte infiltrate around the small vessels, though fungus was not detected in the tissue. Combined therapy with corticosteroid and antifungal agents remarkably improved the neurological symptoms as well as the MRI findings. In the present case, fungal infection possibly induced an altered immune reactions which resulted in the steroid responsive diffuse cerebral white matter lesions.

Anti-Inflammatory Agents↗
PubMed1999

Magnetization transfer ratio of white matter hyperintensities in subcortical ischemic vascular dementia.

BACKGROUND AND PURPOSE: In subjects with subcortical ischemic vascular dementia (SIVD), tissue vacuolization, myelin pallor, and demyelination have been found on pathologic examination of white matter signal hyperintensities (WMSH). Magnetization transfer ratio (MTR) values provide a potential measure of compromised white matter integrity. The purpose of this study was to determine if there were differences in MTR of WMSH between subjects with SIVD and cognitively normal healthy control subjects. METHODS: Fifteen subjects with SIVD and 16 control subjects of comparable age and sex were studied. MTR images were coregistered to MR images segmented into tissue classes (gray matter, white matter, CSF, WMSH, and lacunar infarcts). MTR of WMSH was compared across groups and examined by WMSH location, size, and total burden. RESULTS: WMSH burden was greater in SIVD patients than in control subjects (2.4% vs 0.67%). MTR of WMSH did not differ between groups, but MTR of periventricular WMSH was lower in SIVD patients than in control subjects (37.6% vs 39.4%). Even after accounting for covariant effects of lesion burden, there was still a trend toward reduced periventricular WMSH MTR in the group with dementia. There was no correlation between WMSH MTR and WMSH lesion size. CONCLUSION: These findings are consistent with observations that pathologic changes in vascular dementia are most severe in the periventricular white matter and suggest that insight into the pathophysiology of SIVD might be gleaned from studies of the periventricular region.

Aged↗
PubMed1999

Cerebral white matter lesions in primary Sjögren's syndrome: a controlled study.

OBJECTIVE: To determine the prevalence of neurological and magnetic resonance imaging (MRI) abnormalities in a well defined population of unselected patients with primary Sjögren's syndrome (SS) and age and sex matched healthy patients. METHODS: Thirty patients with SS and 29 age and sex matched controls were examined by a neurologist and subsequently underwent MRI scanning with a 1.0 Tesla Siemens Impact MR scanner. Scans were graded by a neuroradiologist blinded to the clinical status of each subject. The number and location of white matter lesions > 3 mm in long axis (to exclude non-specific perivascular changes) were recorded for each subject. RESULTS: There was a significant increase in lesions detected by MRI in SS patients versus controls (p = 0.02) including deep white matter lesions (p = 0.03) and subcortical white matter lesions (p = 0.02). The presence of white matter lesions did not correlate with serum IgG or rheumatoid factor levels, or with presence of anticardiolipin antibodies. No subjects had symptoms or signs of serious neurological disease including multiple sclerosis, and corpus callosal lesions commonly seen in multiple sclerosis were notably absent in this study. CONCLUSION: Cerebral white matter lesions detected by MRI are more frequent in patients with primary SS than control subjects, yet do not appear to be associated with significant clinical manifestations. Although the pathological nature of these lesions is yet to be defined, their presence should not be over-interpreted.

Adult↗
PubMed1999

Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord.

We have recently reported that minimally disturbed adult CNS white matter can support regeneration of adult axons by using a novel microtransplantation technique to inject minute volumes of dissociated adult rat dorsal root ganglion neurons directly into adult rat CNS pathways (Davies et al., 1997). This atraumatic injection procedure minimized scarring and allowed considerable numbers of regenerating adult axons immediate access to the adult CNS glial terrain where they rapidly extended for long distances. A critical question remained as to whether degenerating white matter at acute and chronic stages (up to 3 months) after injury could still support regeneration. To investigate this, we have microtransplanted adult sensory neurons into degenerating white matter of the adult rat spinal cord several millimeters rostral to a severe lesion of the dorsal columns. Regeneration of donor sensory axons in both directions away from the site of transplantation was robust even within white matter undergoing fulminant Wallerian degeneration despite intimate contact with myelin. Along their route, the regrowing axons extended large numbers of collaterals into the adjacent dorsal horn. However, after entering the lesion, the rapidly extending growth cones stopped and became dystrophic within high concentrations of reactive glial matrix. Our results offer compelling evidence that the major environmental impediment to regeneration in the adult CNS is the molecular barrier that forms directly at the lesion site, and that degenerating white matter beyond the glial scar has a far greater intrinsic ability to support axon regeneration than previously thought possible.

Animals↗
PubMed1999

Identification, isolation, and promoter-defined separation of mitotic oligodendrocyte progenitor cells from the adult human subcortical white matter.

Previous studies have suggested the persistence of oligodendrocyte progenitor cells in the adult mammalian subcortical white matter. To identify oligodendrocyte progenitors in the adult human subcortical white matter, we transfected dissociates of capsular white matter with plasmid DNA bearing the gene for green fluorescence protein (hGFP), placed under the control of the human early promoter (P2) for the oligodendrocytic protein cyclic nucleotide phosphodiesterase (P/hCNP2). Within 4 d after transfection with P/hCNP2:hGFP, a discrete population of small, bipolar cells were noted to express GFP. These cells were A2B5-positive (A2B5(+)), incorporated bromodeoxyuridine in vitro, and constituted <0.5% of all cells. Using fluorescence-activated cell sorting (FACS), the P/hCNP2-driven GFP(+) cells were then isolated and enriched to near-purity. In the weeks after FACS, most P/hCNP2:hGFP-sorted cells matured as morphologically and antigenically characteristic oligodendrocytes. Thus, the human subcortical white matter harbors mitotically competent progenitor cells, which give rise primarily to oligodendrocytes in vitro. By using fluorescent transgenes of GFP expressed under the control of an early oligodendrocytic promoter, these oligodendrocyte progenitor cells may be extracted and purified from adult human white matter in sufficient numbers for implantation and cell-based therapy.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2000

Cognitive dysfunctions and white matter lesions in patients with bipolar disorder in remission.

OBJECTIVE: To compare cognitive functioning in relation to white matter lesions in bipolar disorder in remission and schizophrenia. METHOD: Cognitive performance and the occurrence of white matter lesions on MRI images of the brain were assessed in 22 patients with bipolar disorder in remission, 22 patients with schizophrenia and 22 healthy volunteers. RESULTS: Performance of tests of memory, speed and cognitive flexibility was significantly impaired in both patient groups. The frequency of white matter lesions did not differ significantly between the three groups. No differences in cognitive performance were found between patients with white matter lesions and patients without such lesions. CONCLUSION: White matter lesions apparently do not underlie cognitive deficits that are found in patients with bipolar disorder in remission and in patients with schizophrenia.

Bipolar Disorder↗
PubMed2000

In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism.

BACKGROUND: Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers. METHODS: This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients. RESULTS: The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C. CONCLUSIONS: These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.

Adult↗
PubMed2001

Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury.

Hypoxic-ischemic injury to the periventricular cerebral white matter [periventricular leukomalacia (PVL)] results in cerebral palsy and is the leading cause of brain injury in premature infants. The principal feature of PVL is a chronic disturbance of myelination and suggests that oligodendrocyte (OL) lineage progression is disrupted by ischemic injury. We determined the OL lineage stages at risk for injury during the developmental window of vulnerability for PVL (23-32 weeks, postconceptional age). In 26 normal control autopsy human brains, OL lineage progression was defined in parietal white matter, a region of predilection for PVL. Three successive OL stages, the late OL progenitor, the immature OL, and the mature OL, were characterized between 18 and 41 weeks with anti-NG2 proteoglycan, O4, O1, and anti-myelin basic protein (anti-MBP) antibodies. NG2+O4+ late OL progenitors were the predominant stage throughout the latter half of gestation. Between 18 and 27 weeks, O4+O1+ immature OLs were a minor population (9.9 +/- 2.1% of total OLs; n = 9). Between 28 and 41 weeks, an increase in immature OLs to 30.9 +/- 2.1% of total OLs (n = 9) was accompanied by a progressive increase in MBP+ myelin sheaths that were restricted to the periventricular white matter. The developmental window of high risk for PVL thus precedes the onset of myelination and identifies the late OL progenitor as the major potential target. Moreover, the decline in incidence of PVL at approximately 32 weeks coincides with the onset of myelination in the periventricular white matter and suggests that the risk for PVL is related to the presence of late OL progenitors in the periventricular white matter.

Antigens, Differentiation↗