Degree Of White Matter Damage Research Articles

Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system

HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments that continue to affect approximately half of all HIV-positive individuals despite effective viral suppression through antiretroviral therapy (ART). White matter pathologies have persisted in the ART era, and the degree of white matter damage correlates with the degree of neurocognitive impairment in patients with HAND. The HIV protein Nef has been implicated in HAND pathogenesis, but its effect on white matter damage has not been well characterized. Here, utilizing in vivo, ex vivo, and in vitro methods, we demonstrate that Nef-containing extracellular vesicles (Nef EVs) disrupt myelin sheaths and inflict damage upon oligodendrocytes within the murine central nervous system. Intracranial injection of Nef EVs leads to reduced myelin basic protein (MBP) staining and a decreased number of CC1 + oligodendrocytes in the corpus callosum. Moreover, cerebellar slice cultures treated with Nef EVs exhibit diminished MBP expression and increased presence of unmyelinated axons. Primary mixed brain cultures and enriched oligodendrocyte precursor cell cultures exposed to Nef EVs display a decreased number of O4 + cells, indicative of oligodendrocyte impairment. These findings underscore the potential contribution of Nef EV-mediated damage to oligodendrocytes and myelin maintenance in the pathogenesis of HAND.

Enriched environment enhanced the astrocyte-derived BDNF and VEGF expression and alleviate white matter injuries of rats with ischemic stroke

ABSTRACT Objectives Numerous studies have shown that an enriched environment can promote ischemic stroke and improve cognitive function. In addition, white matter is closely related to cognitive function. The effects and mechanisms of the enriched environment on white matter recovery after stroke have not been elucidated. This study will analyse the effects of the enriched environment on white matter and cognitive function in the post-stroke brain from the perspective of astrocytes and their secretions. Methods Stroke models were used for middle cerebral artery occlusion model. post-operative rats were divided into sham-operated, standard and enriched environment groups. The degree of cerebral infarction was assessed by TTC staining and the degree of white matter damage was assessed by Luxol-Fast Blue staining. The prognosis after stroke was assessed using the longa score and Morris water maze test. Western Blot and immunofluorescence were used to quantify and localize astrocytes and their associated secretory factors and myelin protein markers. Results We found that ischemic stroke can cause severe demyelination. After EE treatment, there was a significant increase in cerebral remyelination and a significant improvement in neurological and cognitive functions. Astrocyte, BDNF, and VEGF expression were significantly higher than in rats in the standard circumstances of stroke model. Conclusion These data suggest that the enriched environment contributes to brain white matter recovery and improvement of cognitive function after stroke. The mechanism is related to astrocytes and their secretions. EE can activate astrocytes to secrete BDNF and VEGF, which may be crucial to promote white matter recovery.

Transcutaneous Auricular Vagus Nerve Stimulation Promotes White Matter Repair and Improves Dysphagia Symptoms in Cerebral Ischemia Model Rats.

BackgroundClinical and animal studies have shown that transcutaneous auricular vagus nerve stimulation (ta-VNS) exerts neuroprotection following cerebral ischemia. Studies have revealed that white matter damage after ischemia is related to swallowing defects, and the degree of white matter damage is related to the severity of dysphagia. However, the effect of ta-VNS on dysphagia symptoms and white matter damage in dysphagic animals after an ischemic stroke has not been investigated.MethodsMiddle cerebral artery occlusion (MCAO) rats were randomly divided into the sham, control and vagus nerve stimulation (VNS) group, which subsequently received ta-VNS for 3 weeks. The swallowing reflex was measured once weekly by electromyography (EMG). White matter remyelination, volume, angiogenesis and the inflammatory response in the white matter were assessed by electron microscopy, immunohistochemistry, stereology, enzyme-linked immunosorbent assay (ELISA) and Western blotting.Resultsta-VNS significantly increased the number of swallows within 20 s and reduced the onset latency to the first swallow. ta-VNS significantly improved remyelination but did not alleviate white matter shrinkage after MCAO. Stereology revealed that ta-VNS significantly increased the density of capillaries and increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) expression in the white matter. ta-VNS significantly alleviated the increase inTLR4, MyD88, phosphorylated MAPK and NF-κB protein levels and suppressed the expression of the proinflammatory factors IL-1β and TNF-α.ConclusionThese results indicated ta-VNS slightly improved dysphagia symptoms after ischemic stroke, possibly by increasing remyelination, inducing angiogenesis, and inhibiting the inflammatory response in the white matter of cerebral ischaemia model rats, implying that ta-VNS may be an effective therapeutic strategy for the treatment of dysphagia after ischemic stroke.

Prognostic value of brain abnormalities for cognitive functioning in cerebral palsy: A prospective cohort study.

Brain abnormalities in cerebral palsy (CP) are known to relate to motor outcome; however, their association with cognitive functioning is less clear. 1) To investigate the prognostic value of brain abnormalities for cognitive functioning; 2) To explore the added value of prognostic variables across ICF domains: motor function, epilepsy, gestational age, birthweight and educational level of the parents. We retrospectively analyzed brain MRI scans of 75 children with CP (GMFCS level I-V, 36% born preterm), as part of a longitudinal study. MRI classification: qualitative classification of brain abnormality pattern and semi-quantitative grading of the extent of damage. Cognitive functioning, measured as non-verbal intelligent quotient (IQ), was dichotomized into 'impaired cognition' (IQ≤70) and 'normal' (IQ>70). Multivariable logistic regression produced odds ratios (OR) with 95% confidence interval (C.I.) of risk factors for impaired cognition. Overall, 27% of the tested participants had a non-verbal IQ below 70 and 36% of the participants was classified as 'having impaired cognition'. At a young age, a higher degree of white matter damage (OR 1.6, 95% C.I. 0.97-2.67) and a more severe GMFCS level (OR 3.2, 95% C.I. 1.70-5.98) are risk factors for impaired cognition at school-age (4-7 years of age). This model correctly predicts 89% of the cases. Brain damage alone predicts the presence of impaired cognition in 71% of the cases. Brain MRI characteristics and GMFCS level at a young age can each help identify children with CP at risk for impaired cognition at school age and together have a strong predictive value.

Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse.

Chronic exposure to high circulating levels of glucocorticoids has detrimental effects on health, including metabolic abnormalities, as exemplified in Cushing’s syndrome (CS). Magnetic resonance imaging (MRI) studies have found volumetric changes in gray and white matter of the brain in CS patients during the course of active disease, but also in remission. In order to explore this further, we performed MRI-based brain volumetric analyses in the AdKO mouse model for CS, which presents its key traits. AdKO mice had reduced relative volumes in several brain regions, including the corpus callosum and cortical areas. The medial amygdala, bed nucleus of the stria terminalis, and hypothalamus were increased in relative volume. Furthermore, we found a lower immunoreactivity of myelin basic protein (MBP, an oligodendrocyte marker) in several brain regions but a paradoxically increased MBP signal in the male cingulate cortex. We also observed a decrease in the expression of glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) and ionized calcium-binding adapter molecule 1 (IBA1, a marker for activated microglia) in the cingulate regions of the anterior corpus callosum and the hippocampus. We conclude that long-term hypercorticosteronemia induced brain region-specific changes that might include aberrant myelination and a degree of white matter damage, as both repair (GFAP) and immune (IBA1) responses are decreased. These findings suggest a cause for the changes observed in the brains of human patients and serve as a background for further exploration of their subcellular and molecular mechanisms.

New Analysis Suggests There Is No Such Thing as Harmless Head Contact in Football

New Analysis Suggests There Is No Such Thing as Harmless Head Contact in Football

Association between Cystatin C and SVD in Chinese population.

Leukoaraiosis is an important clinical feature of cerebral small vessel disease. To date, there is no reliable biomarker to reflect the degree of cerebral small vessel disease and white matter damage. This study aimed to explore the relationship between cystatin C levels and the degree of white matter damage in order to assess whether cystatin C could serve as a biomarker for white matter damage. We conducted a retrospective analysis of 408 non-critically ill hospitalized patients. The included patients underwent related biochemical and cerebral magnetic resonance imaging examinations. The magnetic resonance imaging results were assessed using the Fazekas scale in fluid attenuation inversion recovery imaging. We analyzed the association of each risk factor (sex, age, blood glucose, blood lipid, and cystatin C) with the degree of white matter damage using univariate logistic and multivariate cumulative odds logistic regression (stepwise). Serum cystatin C concentration was closely associated with the degree of white matter damage (odds ratio = 2.14), while age, sex, and hypertension were associated with selective damage of brain white matter. Triglycerides and apolipoprotein A may have a protective effect against white matter damage.

Relation between brain temperature and white matter damage in subacute carbon monoxide poisoning.

In the previous studies, carbon monoxide (CO) poisoning showed an imbalance between cerebral perfusion and metabolism in the acute phase and the brain temperature (BT) in these patients remained abnormally high from the acute to the subacute phase. As observed in chronic ischemic patients, BT can continuously remain high depending on impairments of cerebral blood flow and metabolism; this is because heat removal and production system in the brain may mainly be maintained by the balance of these two factors; thus, cerebral white matter damage (WMD) affecting normal metabolism may affect the BT in patients with CO poisoning. Here, we investigated whether the BT correlates with the degree of WMD in patients with subacute CO-poisoning. In 16 patients with subacute CO-poisoning, the BT and degree of WMD were quantitatively measured by using magnetic resonance spectroscopy and the fractional anisotropy (FA) value from diffusion tensor imaging dataset. Consequently, the BT significantly correlated with the degree of WMD. In particular, BT observed in patients with delayed neuropsychiatric sequelae, a crucial symptom with sudden-onset in the chronic phase after CO exposure, might indicate cerebral hypo-metabolism and abnormal hemodynamics like “matched perfusion,” in which the reduced perfusion matches the reduced metabolism.

White matter tract damage in the behavioral variant of frontotemporal and corticobasal dementia syndromes.

The phenotypes of the behavioral variant of frontotemporal dementia and the corticobasal syndrome present considerable clinical and anatomical overlap. The respective patterns of white matter damage in these syndromes have not been directly contrasted. Beyond cortical involvement, damage to white matter pathways may critically contribute to both common and specific symptoms in both conditions. Here we assessed patients with the behavioral variant of frontotemporal dementia and corticobasal syndrome with whole-brain diffusion tensor imaging to identify the white matter networks underlying these pathologies. Twenty patients with the behavioral variant of frontotemporal dementia, 19 with corticobasal syndrome, and 15 healthy controls were enrolled in the study. Differences in tract integrity between (i) patients and controls, and (ii) patients with the corticobasal syndrome and the behavioral variant of frontotemporal dementia were assessed with whole brain tract-based spatial statistics and analyses of regions of interest. Behavioral variant of frontotemporal dementia and the corticobasal syndrome shared a pattern of bilaterally decreased white matter integrity in the anterior commissure, genu and body of the corpus callosum, corona radiata and in the long intrahemispheric association pathways. Patients with the behavioral variant of frontotemporal dementia showed greater damage to the uncinate fasciculus, genu of corpus callosum and forceps minor. In contrast, corticobasal syndrome patients had greater damage to the midbody of the corpus callosum and perirolandic corona radiata. Whereas several compact white matter pathways were damaged in both the behavioral variant of frontotemporal dementia and corticobasal syndrome, the distribution and degree of white matter damage differed between them. These findings concur with the distinctive clinical manifestations of these conditions and may improve the in vivo neuroanatomical and diagnostic characterization of these disorders.

Toward Objective Markers of Concussion in Sport: A Review of White Matter and Neurometabolic Changes in the Brain after Sports-Related Concussion

Abstract Sports-related concussion is an issue that has piqued the public's attention of late as concerns surrounding potential long-term sequelae as well as new methods of characterizing the effects of this form of injury continue to develop. For the most part, diagnosis of concussion is based on subjective clinical measures and thus is prone to under-reporting. In the current environment, where conventional imaging modalities, such as computed tomography and magnetic resonance imaging, are unable to elucidate the degree of white matter damage and neurometabolic change, a discussion of two advanced imaging techniques-diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS)-is undertaken with a view to highlighting their potential utility. Our aim is to outline a variety of the approaches to concussion research that have been employed, with special attention given to the clinical considerations and acute complications attributed to concussive injury. DTI and MRS have been at the forefront of research as a result of their noninvasiveness and ease of acquisition, and hence it is thought that the use of these neuroimaging modalities has the potential to aid clinical decision making and management, including guiding return-to-play protocols.

Mechanism underlying the protective effect of Kaixin Jieyu Fang on vascular depression following cerebral white matter damage.

The Chinese compound Kaixin Jieyu Fang can be used to treat vascular depression; however, the underlying mechanism remains unclear. This study established a rat model of chronic cerebral ischemia-caused white matter damage by ligation of the bilateral common carotid arteries. Rats received daily intragastric administration of a suspension of Kaixin Jieyu Fang powder. After 3, 7 and 21 days of treatment, the degree of white matter damage in the cerebral ischemia rat model was alleviated, Bcl-2 protein and mRNA expression in brain tissue increased, and Bax protein and mRNA expression decreased. These results indicate that Kaixin Jieyu Fang can alleviate cerebral white matter damage, and the underlying mechanism is associated with regulation of Bcl-2/Bax protein and mRNA expression, which is one of possible mechanism behind the protective effect of Kaixin Jieyu Fang against vascular depression.

Correlating Quantitative MR Imaging with Histopathology in X-Linked Adrenoleukodystrophy

Quantitative MR imaging techniques may improve the pathologic specificity of MR imaging regarding white matter abnormalities. Our purposes were to determine whether ADC, FA, MTR, and MRS metabolites correlate with the degree of white matter damage in patients with X-ALD; whether differences in ADC, FA, and MTR observed in vivo are retained in fresh and formalin-fixed postmortem brain tissue; and whether the differences predict histopathology. MRS metabolites, MTR, ADC, and FA, were determined in 7 patients with X-ALD in 3 white matter areas (NAWM, active demyelination, and complete demyelination) and were compared with values obtained in 14 controls. MTR, ADC, and FA were assessed in postmortem brains from 15 patients with X-ALD and 5 controls. Values were correlated with the degree of astrogliosis and density of myelin, axons, and cells. Equations to estimate histopathology from MR imaging parameters were calculated by linear regression analysis. MRS showed increased mIns, Lac, and Cho and decreased tNAA in living patients with X-ALD; the values depended on the degree of demyelination. MTR, ADC, and FA values were different in postmortem than in vivo white matter, but differences related to degrees of white matter damage were retained. ADC was high and FA and MTR were low in abnormal white matter. Correlations between histopathologic findings and MR imaging parameters were strong. A combination of ADC and FA predicted pathologic parameters best. Changes in quantitative MR imaging parameters, present in living patients and related to the severity of white matter pathology, are retained in postmortem brain tissue. MR imaging parameters predict white matter histopathologic parameters.

442: Magnesium sulfate fails to offer neuroprotection during prenatal exposure to hypoxia in rats

442: Magnesium sulfate fails to offer neuroprotection during prenatal exposure to hypoxia in rats

Effect of dexamethasone on myelin basic protein (MBP) in brain tissues after hypoxic-ischemic brain damage

Objective To explore the possible mechanisms of the neuroprotective effect of dexamethasone(DEX) on neonatal rats with cerebral bypoxia-ischemia. Methods Sprague-Dawley (SD) pregnant rats were made to hypoxic ischemic brain damage (HIBD) model and randomly divided into: pretreatment groups of different doses (L-Dexl group, H-Dexl group); treatment groups of different doses (L-Dex2 group, H-Dex2 group); isotonic saline group (NS group) and normal group (NOR). The expressions of interleukin-1β(IL-1β) and myelin basic protein (MBP) in serum and brain tissue were measured, the number of apoptosis cells in brain tissue was counted, and the pathological changes of brain tissue in HIBD were observed. Results Compared with the NS group, the pathological changes of brain tissue in the pretreatment and treatment groups with different DEX doses were mild with neuron dendrite involution and Nissl body increase. The contents of MBP, IL-1β in serum and brain tissue in NS group 3 days after HIBD were (5.88 4±0. 46,34.25± 4. 65 ; 127. 97± 16.60,1060. 33±42.22)and the numbers of apoptosis were 13.27±0. 90 and 11.05±1.23, which were significantly higher than the NOR group (2.01±0. 12,10. 24±1.75; 41.21±4. 02,221.10± 30. 57; 0. 75±0. 17,P<0. 05). On 7 days after HIBD, the above parameters were decreased in the NS group, but remained higher than the NOR group (P<0. 05). The contents of MBP and IL-1β in in serum and brain Dex pretreated rats were (4. 30±0. 73,24. 10±3. 36,and 59. 89±6. 16,393. 68±31.46) and those in the treated groups(4. 48±0. 49,16. 98±1.32 and 50. 81±8. 32,405. 15±29. 02) were significantly lower than those in the NS group(5.88±0. 46,34. 25±4. 65 and 127.97±16. 60,1060. 33 ±42. 22,P<0. 05). No significant difference was shown between Dexl and Dex2 groups with the same dose. The apoptosis cell count in DEX pretreated and treated groups(7. 92± 1.64 and 8. 97± 0.81) were significantly less than those in the NS group (13. 27±0. 90, P<0. 05). Compared with thc pretreated groups, levels of apoptosis in treated groups were higher (P<0.05) and was dose dependent. Conclusions Variations of serum MBP reflect the degree of white matter damage. DEX might protect the brain from injury by inhibiting overexpression of IL-1β followed by alleviated systemic inflammatory reactions. Key words: Hypoxia-ischemia, brain; Dexamethasone; Apoptosis; Myelin basic proteins; Interleukin-1

Delayed cognitive, behavioral, and radiological changes related to canial irradiation for pediatric brain tumors

20023 Purpose: To evaluate the delayed adverse changes in neuro-cognitive functions as well as white matter damage in radiated survivors of pediatric brain tumors. Methods: Forty two children (22 males) with primary brain tumors who were only treated with cranial radiation, were recruited. 28 patients were treated for low risk medulloblastoma, 10 patients for low grade astrocytoma, 3 patients for low grade ependymoma, and 1 patient for craniopharyngioma. Their ages ranged from 3 to 18 years (mean 10.3±3.98 years).They were subjected, initially just before radiotherapy and at follow-up 1–2 year after completion of cranial radiation, to serial clinical and neuropsychological assessments including Wechseler Intelligence Scale for Children, Vineland social maturity test, Benton Visual Memory Test, and Revised Behavior Problem Checklist. Magnetic resonance scans were also performed to detect the presence of white matter damage before radiotherapy and at follow up. Results: Initially, after surgery and before radiation, intelligence test scores were below normal scores for age and this was of high statistical significance (Total IQ: t= -3.02, P= 0.006). Visual memory test showed evidence of organicity in all cases. Social maturity showed a statistically significant decline as well (t= -2.11, P= 0.04). Follow-up after radiotherapy showed further decline with high statistical significance (Total IQ t= 3.228, P=0.003; visual memory t= 4.08, P= 0.001); An attentional problem has emerged (t= -6.12, P= 0.00). Both radiation dose and volume of radiation showed negative and statistically significant correlation with IQ. Age at diagnosis correlated positively and significantly with IQ ( r= 0.601, P=0.001). Multiple linear regression showed impaired neurocognitive function which was correlated with the degree of white matter damage. (standardized B= -0.577, P= 0.001) and young age at diagnosis (standardized B= -0.427, P= 0.014). Conclusions: Cranial radiation in pediatric brain tumors is associated with a decline in multiple neurocognitive functions including total IQ, visual memory, and attention; which are related to the toxic effect of cranial radiation on white matter of the brain especially in young age of childhood with high dose and whole cranial radiation. No significant financial relationships to disclose.

White matter microstructural abnormalities in late-life depression

To evaluate the location and the degree of white matter damage in late-life depression using diffusion tensor imaging (DTI). Thirty-one patients with late-life depression and 15 healthy volunteers matched for age, gender and years of education received conventional MRI (magnetic resonance imaging) and MR-diffusion tensor scanning. The fractional anisotropy (FA) values of white matter were measured respectively in frontal and temporal regions and the corpus callosum. FA values were significantly decreased in the frontal (superior and middle frontal gyrus), and temporal (right parahippocampal gyrus) regions of elderly patients with depression compared with healthy controls. Microstructural changes in the frontal (superior and middle frontal gyrus) and temporal (right parahippocampal gyrus) areas are associated with late-life depression.