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PubMed1996

Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter.

OBJECTIVES: To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS: Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS: Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups. CONCLUSIONS: Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.

Aged↗
PubMed1999

White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging.

OBJECTIVES: Alzheimer's disease and vascular dementia are associated with an increase in changes in white matter on MRI. The aims were to investigate whether white matter changes also occur in dementia with Lewy bodies and to examine the relation between white matter lesions and the cognitive and non-cognitive features of dementia with Lewy bodies, Alzheimer's disease, and vascular dementia. METHODS: Proton density and T2 weighted images were obtained on a 1.0 Tesla MRI scanner in patients with dementia with Lewy bodies (consensus criteria; n=27, mean age=75.9 years), Alzheimer's disease (NINCDS/ADRDA; n=28, mean age=77.4 years), vascular dementia (NINDS/AIREN; n=25, mean age=76.8 years), and normal controls (n=26, mean age=76.2 years). Cognitive function, depressive symptoms, and psychotic features were assessed using a standardised protocol. Periventricular hyperintensities (PVHs), white matter hyperintensities (WMHs) and basal ganglia hyperintensities (BGHs) were visually rated blind to diagnosis using a semiquantitative scale. RESULTS: Periventricular hyperintensities were positively correlated with age and were more severe in all dementia groups than controls. Total deep hyperintensities scores (WMHs plus BGHs) were significantly higher in all dementia groups than controls and higher in patients with vascular dementia than those with dementia with Lewy bodies or Alzheimer's disease. In all patients with dementia, frontal WMHs were associated with higher depression scores and occipital WMHs were associated with an absence of visual hallucinations and delusions. CONCLUSION: In common with Alzheimer's disease and vascular dementia, PVHs and WMHs were significantly more extensive in dementia with Lewy bodies than in controls. This overlap between different dementias may reflect shared pathological mechanisms. The link between frontal WMHs and depression and the absence of occipital WMHs and psychotic symptoms has important implications for understanding the neurobiological basis of these symptoms.

Aged↗
PubMed2000

In vivo investigation of white matter pathology in schizophrenia with magnetisation transfer imaging.

OBJECTIVES: This study is the first to use magnetisation transfer imaging (MTI), a technique sensitive to myelin and axonal abnormalities, to investigate the white matter in vivo in patients with schizophrenia. METHODS: MTI was performed in 25 schizophrenic patients and 30 healthy controls. A region of interest (ROI) approach was used to obtain magnetisation transfer ratios (MTRs) in several regions of cerebral white matter. RESULTS: MTR values were significantly reduced in the right and left temporal regions in schizophrenic patients compared with controls (p<0.001). Clinical variables such as age, duration of symptoms, schizophrenic symptomatology, and soft neurological signs did not predict this reduction in MTR. There were no MTR abnormalities in the other regions sampled. However, the correlation between the left and right frontal MTR values was marginally significantly different in schizophrenic patients compared with controls suggesting that subtle differences in interhemispheric connections may be present. CONCLUSIONS: Subtle white matter pathology, most likely related to myelin and axonal abnormalities, can be detected in the temporal lobes in schizophrenic patients. MTI may be a useful tool in investigating the white matter in schizophrenia.

Adult↗
PubMed2000

Reduction of frontal neocortical grey matter associated with affective aggression in patients with temporal lobe epilepsy: an objective voxel by voxel analysis of automatically segmented MRI.

BACKGROUND: Interictal episodes of aggression are often reported in patients with epilepsy. Some have characteristics of what has been referred to as episodic dyscontrol or intermittent explosive disorder (IED). Although structural brain abnormalities are thought to play a part in the pathophysiology of aggression, there are few in vivo studies of structural cerebral changes in patients with epilepsy and aggression. Using quantitative MRI, subtle structural brain abnormalities can be investigated in subgroups of patients with both epilepsy and episodes of affective aggression. METHODS: After automated segmentation of cerebral grey matter from T1 weighted MRI, the objective technique of statistical parametric mapping (SPM) was applied to the analysis of 35 control subjects, 24 patients with temporal lobe epilepsy (TLE) with a history of repeated, interictal episodes of aggression, and 24 patients with TLE without episodes of aggression. Both TLE patient groups were compared with each other and with the control subjects on a voxel by voxel basis for increases and decreases of grey matter. RESULTS: The patients with TLE with aggressive episodes had a decrease of grey matter, most markedly in the left frontal lobe, compared with the control group and with patients with TLE without aggressive episodes. CONCLUSION: These findings suggest that a reduction of frontal neocortical grey matter might underly the pathophysiology of aggression in TLE. These voxel by voxel comparisons can guide further in vivo studies into aggression.

Adolescent↗
PubMed2001

Cerebral metabolic impairment in patients with obstructive sleep apnoea: an independent association of obstructive sleep apnoea with white matter change.

OBJECTIVES: To determine the relation between severity of obstructive sleep apnoea (OSA) and degree of cerebral metabolic impairment. METHODS: Fifty five patients with habitual snoring and excessive daytime sleepiness underwent standard overnight polysomnography and magnetic resonance spectroscopy separately. Proton MR spectra were measured with two dimensional chemical shift imaging (repetition time; 1500 ms, echo time; 135 ms). Severity of cerebral metabolic impairment was assessed by the N-acetylaspartate (NAA)/choline ratios for the cerebral cortex and white matter. Severity of OSA was assessed by the apnoea-hypopnoea index (AHI) and the minimum value of peripheral oxyhaemoglobin saturation. All patients were evaluated for the presence or absence of comobidities including hypertension, cardiac disease, diabetes mellitus, and hyperlipidaemia. Univariate analysis of variance (ANOVA) and mulitple linear regression analysis were used for statistical analyses. RESULTS: Univariate ANOVA disclosed significant effects of AHI, age, and the presence or absence of hypertension on the NAA/choline ratio for cerebral white matter (p=0.011, p=0.028, p=0.0496, respectively). The AHI had a significant negative association with the NAA/choline ratio for cerebral white matter, independent of age and the presence or absence of cardiac disease, in the final multivariate regression model (standardised partial regression coefficient=-0.417, p<0.001). No significant relation was found between severity of OSA and the NAA/choline ratio for the cerebral cortex. Age alone had a significant effect on the NAA/choline ratio for the cerebral cortex on univariate ANOVA (p<0.001) and a significant negative association with the NAA/choline ratio for the cerebral cortex in the regression model (r=-0.552, p<0.001). CONCLUSIONS: A significant relation exists between AHI and the degree of metabolic impairment in cerebral white matter in patients with OSA.

Adult↗
PubMed2001

Magnetisation transfer ratio analysis of normal appearing white matter in patients with familial and sporadic multiple sclerosis.

OBJECTIVES: To assess differences in magnetisation transfer ratio (MTR) analysis of normal appearing white matter (NAWM) in patients with familial multiple sclerosis (MS) and those with sporadic MS. METHODS: 10 patients with familial MS, 10 patients with sporadic MS, and 10 healthy subjects were included in the study. Groups were matched according to the sex, age, disease duration, type of disease, EDSS, and MRI T1 and T2 lesion load. Magnetisation transfer imaging (MTI) with and without saturation pulse were performed. On the MTR map 16 different regions of interest of normal appearing white matter were analyzed. RESULTS: The mean MTR value of normal appearing white matter was significantly lower both in familial patients and those with sporadic MS compared with healthy subjects (33.8% v 46.4%; 38.6% v 46.4% respectively, p< 0.05). Additionally, patients with familial MS showed significantly lower mean MTR value than patients with sporadic MS (33.8% v 38.6%, p<0.05). There was also significant regional variation of MTR values between these two groups of patients. CONCLUSIONS: Lower and more widespread MTR abnormalities in patients with familial MS might indicate differences in the extent and nature of white matter pathology between familial and sporadic MS.

Adult↗
PubMed2002

Voxel based morphometry of grey matter abnormalities in patients with medically intractable temporal lobe epilepsy: effects of side of seizure onset and epilepsy duration.

OBJECTIVES: To investigate the use of whole brain voxel based morphometry (VBM) and stereological analysis to study brain morphology in patients with medically intractable temporal lobe epilepsy; and to determine the relation between side, duration, and age of onset of temporal lobe epilepsy, history of childhood febrile convulsions, and grey matter structure. METHODS: Three dimensional magnetic resonance images were obtained from 58 patients with left sided seizure onset (LSSO) and 58 patients with right sided seizure onset (RSSO), defined using EEG and foramen ovale recordings in the course of presurgical evaluation for temporal lobectomy. Fifty eight normal controls formed a comparison group. VBM was used to characterise whole brain grey matter concentration, while the Cavalieri method of modern design stereology in conjunction with point counting was used to estimate hippocampal and amygdala volume. Age and sex were used as confounding covariates in analyses. RESULTS: LSSO and RSSO patients showed significant reductions in volume (using stereology) and grey matter concentration (using VBM) of the hippocampus, but not of the amygdala, in the presumed epileptogenic zone when compared with controls, but hippocampal (and amygdala) volume and grey matter concentration were not related to duration or age of onset of epilepsy. LSSO and RSSO patients with a history of childhood febrile convulsions had reduced hippocampal volumes in the presumed epileptogenic zone compared with patients without such a history. Left amygdala volume was also reduced in LSSO patients with a history of childhood convulsions. VBM results indicated bilateral thalamic, prefrontal, and cerebellar GMC reduction in patients, which correlated with duration and age of onset of epilepsy. CONCLUSIONS: Hippocampal sclerosis is not necessarily the consequence of recurrent temporal lobe seizures. A major cause of hippocampal sclerosis appears to be an early aberrant neurological insult, such as childhood febrile seizures. Secondary brain abnormalities exist in regions outside the presumed epileptogenic zone and may result from recurrent seizures.

Adolescent↗
PubMed2005

Associations between ambient, personal, and indoor exposure to fine particulate matter constituents in Dutch and Finnish panels of cardiovascular patients.

AIMS: To assess the relation between ambient, indoor, and personal levels of PM2.5 and its elemental composition for elderly subjects with cardiovascular disease. METHODS: In the framework of a European Union funded study, panel studies were conducted in Amsterdam, the Netherlands and Helsinki, Finland. Outdoor PM2.5 concentrations were measured at a fixed site. Each subject's indoor and personal PM2.5 exposure was measured biweekly for six months, during the 24 hour period preceding intensive health measurements. The absorbance of PM2.5 filters was measured as a marker for diesel exhaust. The elemental content of more than 50% of the personal and indoor samples and all corresponding outdoor samples was measured using energy dispersive x ray fluorescence. RESULTS: For Amsterdam and Helsinki respectively, a total of 225 and 238 personal, and 220 and 233 indoor measurements, were analysed from 36 and 46 subjects. For most elements, personal and indoor concentrations were lower than and highly correlated with outdoor concentrations. The highest correlations (median r>0.9) were found for sulfur and particle absorbance, which both represent fine mode particles from outdoor origin. Low correlations were observed for elements that represent the coarser part of the PM2.5 particles (Ca, Cu, Si, Cl). CONCLUSIONS: The findings of this study provide support for using fixed site measurements as a measure of exposure to particulate matter in time series studies linking the day to day variation in particulate matter to the day to day variation in health endpoints, especially for components of particulate matter that are generally associated with fine particles and have few indoor sources. The high correlation for absorbance of PM2.5 documents that this applies to particulate matter from combustion sources, such as diesel vehicles, as well.

Aged↗
PubMed1977

White and gray matter of the brain differentiated by computed tomography.

The white and gray matter of the brain can be clearly differentiated by computed tomography (CT). The differentiation is enhanced by the administration of contrast material. Without contrast material, the mean attenuation number of the white matter was 29 units, of the gray matter, 35 units. The effective low contrast resolving power of CT scanners can be clinically evaluated by comparing their ability to differentiate the white and gray matter of the brain.

Brain↗
PubMed2002

Holoprosencephaly in children: diffusion tensor MR imaging of white matter tracts of the brainstem--initial experience.

PURPOSE: To evaluate the dimensions of specific white matter tracts in the brainstems (region of brain thought to be least affected) of children with holoprosencephaly by using diffusion tensor magnetic resonance (MR) imaging and to correlate these abnormalities with forebrain malformation severity and neurologic deficit severity. MATERIALS AND METHODS: Thirteen patients with holoprosencephaly underwent diffusion tensor MR imaging, with which white matter color maps were generated. Type of holoprosencephaly was correlated with presence or absence of specific brainstem white matter tracts. Furthermore, patient rank based on cortico-ponto-spinal tract (CPST) and middle cerebellar peduncle (MCP) dimensions was correlated with holoprosencephaly type and neurodevelopmental score by using Spearman rank correlation analysis. RESULTS: Two patients had alobar holoprosencephaly, five had the semilobar type, one had the lobar type, and one had the middle-hemisphere-variant type. Four patients were excluded from analysis. In the two patients with alobar holoprosencephaly, the CPSTs were absent bilaterally. In all of the remaining patients except one, who had semilobar holoprosencephaly in which the CPSTs could not be identified at the level of the medulla oblongata, all tracts were present bilaterally. Holoprosencephaly type and neurodevelopmental score correlated strongly with CPST and MCP dimensions (P <.01) over and above the effect of age. CONCLUSION: In vivo identification of brainstem white matter tract abnormalities in patients with holoprosencephaly can be achieved by performing diffusion tensor MR imaging.

Brain Mapping↗
PubMed2004

Pattern of white matter abnormalities at MR imaging: use of polymerase chain reaction testing of Guthrie cards to link pattern with congenital cytomegalovirus infection.

PURPOSE: To define a magnetic resonance (MR) imaging pattern suggestive of congenital cytomegalovirus (CMV) infection by using polymerase chain reaction (PCR) testing to detect CMV DNA in neonatal blood on Guthrie cards for validation. MATERIALS AND METHODS: On the basis of findings in eight patients with documented congenital CMV infection, the authors developed MR imaging inclusion criteria, including multifocal lesions predominantly located in the deep parietal white matter. If gyral abnormalities were present, white matter lesions were either multifocal or diffuse. The criteria were applied to 152 patients with static leukoencephalopathy of unknown etiology. Guthrie cards for 22 of the 43 patients fulfilling the MR imaging criteria, 20 patients not fulfilling them, and 300 control subjects were analyzed. Fisher exact testing was used to evaluate the association between MR imaging characteristics and CMV status, and backward elimination linear discriminant analysis was used to identify MR imaging characteristics predictive of CMV infection in addition to the initial criteria. RESULTS: PCR test results were positive in 12 of 22 patients suspected of having congenital CMV infection, in no patient not suspected of having infection (P <.001), and in two of 300 control subjects (negative predictive value [NPV] of MR imaging criteria, 100% [95% CI: 83%, 100%]; positive predictive value [PPV], 55% [95% CI: 32%, 76%]). The most important additional MR imaging finding predicting a positive PCR result was abnormality of the anterior part of the temporal lobe, including abnormal white matter, cysts, and enlargement of inferior horns. Including this finding in the MR imaging criteria enhanced the PPV (89%; 95% CI: 52%, 99%) at the expense of the NPV (88%; 95% CI: 72%, 97%). CONCLUSION: In patients with static encephalopathy, an MR imaging pattern of multifocal lesions predominantly involving deep parietal white matter, with or without gyral abnormalities, is predictive of congenital CMV infection. When gyral abnormalities are present, leukoencephalopathy may also be diffuse. The presence of abnormalities in the anterior part of the temporal lobe increases the likelihood that CMV infection is present.

Brain↗
PubMed2006

Childhood white matter disorders: quantitative MR imaging and spectroscopy.

PURPOSE: To prospectively investigate whether quantitative magnetic resonance (MR) parameters, including magnetization transfer ratio (MTR), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and MR spectroscopic metabolite concentrations, allow for discrimination between different types of pathologic conditions that underlie signal intensity abnormalities in white matter. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Forty-one patients (19 male, 22 female; mean age, 15.4 years) and 41 control subjects (25 male, 16 female; mean age, 11.3 years) were included. Twelve patients had a hypomyelinating disorder; 14, a demyelinating disorder; five, a disorder characterized by myelin vacuolation; and 10, a disorder characterized by cystic degeneration. Regions of interest were selected within the parietal white matter and were transferred to the corresponding sections of the generated ADC, FA, and MTR maps to extract quantitative measurements. Linear discriminant analysis and univariate analysis of covariance were used for statistical evaluation. RESULTS: Linear discriminant analysis showed that 95% of patients were correctly classified by using total creatine, choline-containing compounds, myo-inositol, MTR, and ADC. In the hypomyelination group, all MR parameters were close to normal, with the exception of elevated total creatine (P = .03) and myo-inositol (P < .001) levels and decreased MTR values (P < .001). In the demyelination group, the levels of choline-containing compounds (P = .02) and myo-inositol (P < .001) were highly elevated. In the myelin vacuolation and cystic degeneration groups, high ADC values (P < .001) and variable decreases in all MR spectroscopic metabolites were seen. MTR was significantly reduced (P < .001) in the cystic degeneration group. CONCLUSION: Quantitative MR techniques can be used to discriminate between different types of white matter disorders and to classify white matter lesions of unknown origin with respect to underlying pathologic conditions.

Adolescent↗
PubMed1981

The evolution of white matter disease as seen on computed tomography.

The evolving computed tomographic (CT) findings in three patients with different types of dysmyelinating white matter diseases (Krabbe, Canavan, ketotic hyperglycinemia) are presented. Serial CT scans suggested that the abnormal, low density white matter, which is characteristic of many white matter diseases, is present for only a limited time, corresponding to active dys- or demyelination. The low density abnormality gives way to a nonspecific final common pathway manifested as severe atrophy on CT. Ventricular enlargement is accentuated in this form of atrophy which appears to be the final stage in a wide variety, if not all, of white matter diseases.

Atrophy↗
PubMed1991

Alzheimer disease: measuring loss of cerebral gray matter with MR imaging.

The distributions of the cerebral gray matter, the white matter, and the intracranial cerebrospinal fluid (CSF) were measured in 14 patients with Alzheimer disease (AD) and in 14 healthy control subjects. The measurements, derived from two specifically designed magnetic resonance inversion-recovery sequences, compensate for partial signal averaging. The percentage of the gray matter in the brains of AD patients (44.9% +/- 4.4) was significantly lower than in control subjects (50.2% +/- 3.2). The most significant reduction (P less than .001) occurred in the temporal lobes (13.8%) and a central region (12.8); the reduction in frontal lobe (11.2%) and occipital lobe (9.2%) was also statistically significant (P less than .01). There was an increase in the CSF volume in the temporal, occipital, and frontal regions; no region showed a significant difference in the white matter content. The findings of diffuse changes and temporal lobe involvement in AD are consistent with pathologic observations of cortical cell loss.

Aged↗
PubMed1991

Transient white matter changes on MR images in children undergoing chemotherapy for acute lymphocytic leukemia: correlation with neuropsychologic deficiencies.

The cranial magnetic resonance (MR) images of 25 children with acute lymphocytic leukemia (ALL) who were undergoing chemotherapy were retrospectively studied to determine the frequency of white matter changes and to analyze the significance of these observed changes in predicting subsequent neuropsychologic deficiencies. MR images showed transient white matter abnormalities in 17 of the 25 patients during consolidation therapy. Twelve of 20 children showed neuropsychologic deficits. There was no correlation between white matter changes and neuropsychologic deficits. In the subgroup of children under age 5 years at the time of diagnosis, 10 of 11 showed neuropsychologic deficits, and eight of 11 had white matter changes. Children under age 5 who undergo chemotherapy for ALL are at high risk to develop neuropsychologic deficiencies. Age at diagnosis is a reliable predictor of subsequent neuropsychologic deficits.

Adolescent↗
PubMed1995

Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements.

PURPOSE: To assess for the presence of microscopic abnormalities in otherwise normal-appearing white matter on T2-weighted images in patients with multiple sclerosis (MS) by using magnetization-transfer (MT) measurements. MATERIALS AND METHODS: Twenty-three patients with MS and nine healthy control subjects underwent magnetic resonance (MR) imaging with a 1.5-T system. MT ratios (MTRs) were measured in 16 areas of normal-appearing white matter identified on conventional T2-weighted images in patients with MS. MTRs in the same white-matter locations in control subjects were determined. The two groups were compared. RESULTS: The mean whole-brain MTR of normal-appearing white matter in patients was 40.13% +/- 1.37 (standard deviation; range, 36.31%-42.09%); in control subjects, 42.93% +/- 0.95 (range, 41.62%-44.50%). The difference was statistically significant (P < or = .001). Except for the internal capsules, the difference in mean MTRs in each sublocation of the brain between patients and control subjects was statistically significant (P < or = .05). CONCLUSION: MT measurements are more sensitive than conventional MR imaging in the detection of abnormalities beyond the resolution of T2-weighted imaging.

Adult↗
PubMed1997

Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study.

PURPOSE: To determine the distribution of changes in sulcal size, ventricular size, and white matter signal intensity depicted on cranial magnetic resonance (MR) images, with stratification according to age, race, and sex. MATERIALS AND METHODS: Ventricular size, sulcal size, and white matter signal intensity changes were graded on cranial MR images of 3,660 community-living, elderly participants in the Cardiovascular Health Study. A healthier subgroup was also defined. Summary statistics for both groups were generated for age, race, and sex. RESULTS: Regression models of the entire imaged cohort showed higher grades of all variables with increasing age, and higher ventricular and sulcal grades in men and in nonblack individuals. White matter grade was greater in women and in black individuals. Regression models of the healthier subgroup showed similar associations, except for a lack of association of sulcal and ventricular size with race. CONCLUSION: Sulcal width, ventricular size, and white matter signal intensity change with age, sex, and race. Knowledge of these changes is important in appropriate interpretation of MR images of the elderly.

Aged↗
PubMed2001

Perinatal hypoxia-ischemia induces apoptotic and excitotoxic death of periventricular white matter oligodendrocyte progenitors.

Hypoxia-ischemia (HI) is a leading cause of white matter damage, a major contributor to cerebral palsy in premature infants. Preferential white matter damage is believed to result from vulnerability of the immature oligodendrocyte (the pro-OL) to factors elevated during ischemic damage, such as oxygen free radicals and glutamate. In order to determine whether pro-OLs undergo apoptotic death after HI, we analyzed periventricular white matter OLs in P7 rats 4, 12 and 24 h after HI to analyze the time course and mode of cell death. DNA fragmentation was seen at 12 and 24 h of recovery after HI, representing a 17-fold increase over control. In addition, caspase-3 activation was found in NG2+ pro-OLs at 12 h. Electron-microscopic analysis of cell death in the white matter revealed a transition from early necrotic deaths to hybrid cell deaths to classical apoptosis between 4 and 24 h of recovery from HI. The delayed time course of apoptosis in pro-OLs supports the feasibility of interventions to improve clinical outcomes for newborns surviving birth asphyxia.

Animals↗