scholarly journals Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain

2022 ◽  
Author(s):  
Anthony Fernandez-Castaneda ◽  
Peiwen Lu ◽  
Anna C Geraghty ◽  
Eric Song ◽  
Myoung-Hwa Lee ◽  
...  
Keyword(s):  
White Matter ◽  
Cancer Therapy ◽  
Subcortical White Matter ◽  
Hippocampal Neurogenesis ◽  
Neurological Symptoms ◽  
Cognitive Symptoms ◽  
Human Brain Tissue ◽  
Cellular Mechanisms ◽  
Speed Of Information Processing ◽  
After Cancer

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection, without neuroinvasion, and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

scholarly journals Breakdown of Calcium Homeostasis in Relation to Tissue Depolarization: Comparison between Gray and White Matter Ischemia

1999 ◽  
Vol 19 (7) ◽  
pp. 788-793 ◽  
Author(s):  
E. Kumura ◽  
R. Graf ◽  
C. Dohmen ◽  
G. Rosner ◽  
W. D. Heiss
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Direct Current ◽  
Subcortical White Matter ◽  
Global Cerebral Ischemia ◽  
Cerebral White Matter ◽  
Cellular Mechanisms ◽  
Current Potential

In vitro studies suggest that ischemic injury of cerebral white matter is mediated by nonsynaptic cellular mechanisms, such as Ca2+ entry into axons through reversal of the Na+-Ca2+ exchanger. The authors investigated extracellular Ca2+ concentration in relation to tissue depolarization (direct current potential) in vivo using ion-selective electrodes in cortical gray and subcortical white matter of α-chloralose-anesthetized cats during 120 minutes of global cerebral ischemia. On induction of ischemia, regional CBF, as measured by hydrogen clearance, ceased. The direct current potential decreased rapidly within minutes in gray matter and with little time delay in white matter. Extracellular Ca2+ concentration decreased just as quickly in gray matter. In white matter, in contrast, extracellular Ca2+ increased in the first 20 to 30 minutes, and a delayed and much slower decline, compared with gray matter, was observed thereafter, reaching a minimal level only about 60 minutes after occlusion. Our results suggest that smaller and delayed transmembrane shifts of Ca2+ are correlates of delayed ischemic membrane dysfunction in central white matter tracts, which may be explained by a lack of synaptic mechanisms.

What Has Direct Cortical and Subcortical Electrostimulation Taught Us about Neurolinguistics?

2019 ◽  
pp. 185-211
Author(s):  
Hugues Duffau
Keyword(s):  
White Matter ◽  
Large Scale ◽  
Functional Neuroimaging ◽  
Great Accuracy ◽  
Subcortical White Matter ◽  
Cerebral Lesions ◽  
Physiological Basis ◽  
Postoperative Mri ◽  
The Brain

Investigating the neural and physiological basis of language is one of the most important challenges in neurosciences. Direct electrical stimulation (DES), usually performed in awake patients during surgery for cerebral lesions, is a reliable tool for detecting both cortical and subcortical (white matter and deep grey nuclei) regions crucial for cognitive functions, especially language. DES transiently interacts locally with a small cortical or axonal site, but also nonlocally, as the focal perturbation will disrupt the entire subnetwork sustaining a given function. Thus, in contrast to functional neuroimaging, DES represents a unique opportunity to identify with great accuracy and reproducibility, in vivo in humans, the structures that are actually indispensable to the function, by inducing a transient virtual lesion based on the inhibition of a subcircuit lasting a few seconds. Currently, this is the sole technique that is able to directly investigate the functional role of white matter tracts in humans. Thus, combining transient disturbances elicited by DES with the anatomical data provided by pre- and postoperative MRI enables to achieve reliable anatomo-functional correlations, supporting a network organization of the brain, and leading to the reappraisal of models of language representation. Finally, combining serial peri-operative functional neuroimaging and online intraoperative DES allows the study of mechanisms underlying neuroplasticity. This chapter critically reviews the basic principles of DES, its advantages and limitations, and what DES can reveal about the neural foundations of language, that is, the large-scale distribution of language areas in the brain, their connectivity, and their ability to reorganize.

Breast carcinoma after cancer therapy in childhood

Cancer ◽  
1983 ◽  
Vol 51 (3) ◽  
pp. 521-523 ◽  
Author(s):  
Frederick P. Li ◽  
Joseph Corkery ◽  
Gordon Vawter ◽  
William Fine ◽  
Stephen E. Sallan
Keyword(s):  
Breast Carcinoma ◽  
Cancer Therapy ◽  
After Cancer

scholarly journals Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity

2021 ◽  
Vol 22 (9) ◽  
pp. 4953
Author(s):  
Natalie M. Zahr ◽  
Kilian M. Pohl ◽  
Allison J. Kwong ◽  
Edith V. Sullivan ◽  
Adolf Pfefferbaum
Keyword(s):  
White Matter ◽  
Proinflammatory Cytokines ◽  
Soluble Protein ◽  
Subcortical White Matter ◽  
Control Group ◽  
White Matter Volume ◽  
Brain Volumes ◽  
Protein Levels ◽  
Matter Volume ◽  
Patient Groups

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.

Diffusion tensor imaging analysis in scrub typhus meningoencephalitis to determine the alteration of microstructural subcortical white-matter integrity

2020 ◽  
pp. 197140092098031
Author(s):  
Pranjal Phukan ◽  
Kalyan Sarma ◽  
Aman Yusuf Khan ◽  
Bhupen Barman ◽  
Md Jamil ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Scrub Typhus ◽  
Diffusion Tensor ◽  
Neuronal Degeneration ◽  
Central Nervous System Involvement ◽  
Subcortical White Matter ◽  
White Matter Integrity ◽  
Conventional Mri ◽  
Significant Difference

Background and purpose Magnetic resonance imaging (MRI) of the brain in scrub typhus meningoencephalitis is non-specific, and in the majority of the cases, conventional MRI fails to detect any abnormality. However, autopsy reports depict central nervous system involvement in almost all patients. There is therefore a need for research on the quantitative assessment of brain parenchyma that can detect microstructural abnormalities. The study aimed to assess the microstructural integrity changes of scrub typhus meningoencephalitis by using different diffusion tensor imaging (DTI) parameters. Methods This was a retrospective analysis of scrub typhus meningoencephalitis. Seven patients and seven age- and sex-matched healthy controls were included. Different DTI parameters such as apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), trace, volume ratio (VR) and geodesic anisotropy (GA) were obtained from six different regions of subcortical white matter at the level of the centrum semiovale. Intergroup significant difference was determined by one-way analysis of variance followed by Tukey’s post hoc test. Receiver operating characteristic curves were constructed to determine the accuracy of the DTI matrices. Results There was a significant decrease in FA, RA and GA as well as an increase in ADC and VR in the subcortical white matter in patients with scrub typhus meningoencephalitis compared to controls ( p < 0.001). The maximum sensitivity of the DTI parameters was 85.7%, and the maximum specificity was 81%. Conclusion There was an alteration of subcortical white-matter integrity in scrub typhus meningoencephalitis that represents the axonal degeneration, myelin breakdown and neuronal degeneration. DTI may be a useful tool to detect white-matter abnormalities in scrub typhus meningoencephalitis in clinical practice, particularly in patients with negative conventional MRI.

scholarly journals Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariano Guardia Clausi ◽  
Alexander M. Stessin ◽  
Zirun Zhao ◽  
Stella E. Tsirka ◽  
Samuel Ryu
Keyword(s):  
Brain Tissue ◽  
Cranial Irradiation ◽  
Subcortical White Matter ◽  
Glioma Cell Line ◽  
Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Long Term Effects ◽  
Normal Brain Tissue ◽  
Molecule Inhibitor

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

Use of an intracranial near-infrared probe for localization during stereotactic surgery for movement disorders

2000 ◽  
Vol 93 (3) ◽  
pp. 498-505 ◽  
Author(s):  
Cole A. Giller ◽  
Maureen Johns ◽  
Hanli Liu
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Movement Disorders ◽  
Near Infrared ◽  
Subcortical White Matter ◽  
Stereotactic Surgery ◽  
Resected Specimen ◽  
Subcortical Structures ◽  
Content Type ◽  
Fine Print

✓ Localization of targets during stereotactic surgery is frequently accomplished by identification of the boundaries between the gray matter of various nuclei and the surrounding white matter. The authors describe an intracranial probe developed for this purpose, which uses near-infrared (NIR) light.The probe fits through standard stereotactic holders and emits light at its tip. The scattered light is detected and analyzed by a spectrometer, with the slope of the trailing portion of the reflectance curve used as the measurement value.Near-infrared readings were obtained during 27 neurosurgical procedures. The first three operations were temporal lobectomies, with values obtained from tracks in the resected specimen and resection bed. In the next five procedures, the probe was inserted stereotactically to a depth of 1 to 2 cm with measurements obtained every 1 mm. The probe was then used in 19 stereotactic procedures for movement disorders, obtaining measurements every 0.5 to 1 mm to target depths of 6 to 8 cm to interrogate subcortical structures. The NIR signals were correlated to distances beneath the cortical surface measured on postoperative computerized tomography or magnetic resonance imaging by using angle correction and three-dimensional reconstruction techniques.The NIR values for white and gray matter obtained during the lobectomies were significantly different (white matter 2.5 ± 0.37, gray matter 0.82 ± 0.23 mean ± standard deviation). The NIR values from the superficial stereotactic tracks showed initial low values corresponding to cortical gray matter and high values corresponding to subcortical white matter.There was good correlation between the NIR signals and postoperative imaging in the 19 stereotactic cases. Dips due to adjacent sulci, a plateau of high signal due to subcortical white matter, a dip in the NIR signal during passage through the ventricle, dips due to the caudate nucleus, and peaks due to the white matter capsule between ventricle and thalamus were constant features. The putamen—capsule boundary and the lamina externa and interna of the globus pallidus could be distinguished in three cases. Elevated signals corresponding to the thalamic floor were seen in 10 cases. Nuances such as prior lesions and nonspecific white matter changes were also detected. There was no incidence of morbidity associated with use of the probe. Data acquisition was straightforward and the equipment required for the studies was inexpensive.The NIR probe described in this article seems to be able to detect gray—white matter boundaries around and within subcortical structures commonly encountered in stereotactic functional neurosurgery. This simple, inexpensive method deserves further study to establish its efficacy for stereotactic localization.

Increased MRI-based cortical grey/white-matter contrast in sensory and motor regions in schizophrenia and bipolar disorder

2016 ◽  
Vol 46 (9) ◽  
pp. 1971-1985 ◽  
Author(s):  
K. N. Jørgensen ◽  
S. Nerland ◽  
L. B. Norbom ◽  
N. T. Doan ◽  
R. Nesvåg ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
White Matter ◽  
Linear Models ◽  
Subcortical White Matter ◽  
Precentral Gyrus ◽  
Average Group ◽  
Medication Dose ◽  
Weighted Magnetic Resonance Imaging ◽  
The Difference ◽  
Magnetic Resonance Imaging Mri

BackgroundSchizophrenia and bipolar disorder share genetic risk factors and one possible illness mechanism is abnormal myelination. T1-weighted magnetic resonance imaging (MRI) tissue intensities are sensitive to myelin content. Therefore, the contrast between grey- and white-matter intensities may reflect myelination along the cortical surface.MethodMRI images were obtained from patients with schizophrenia (n = 214), bipolar disorder (n = 185), and healthy controls (n = 278) and processed in FreeSurfer. The grey/white-matter contrast was computed at each vertex as the difference between average grey-matter intensity (sampled 0–60% into the cortical ribbon) and average white-matter intensity (sampled 0–1.5 mm into subcortical white matter), normalized by their average. Group differences were tested using linear models covarying for age and sex.ResultsPatients with schizophrenia had increased contrast compared to controls bilaterally in the post- and precentral gyri, the transverse temporal gyri and posterior insulae, and in parieto-occipital regions. In bipolar disorder, increased contrast was primarily localized in the left precentral gyrus. There were no significant differences between schizophrenia and bipolar disorder. Findings of increased contrast remained after adjusting for cortical area, thickness, and gyrification. We found no association with antipsychotic medication dose.ConclusionsIncreased contrast was found in highly myelinated low-level sensory and motor regions in schizophrenia, and to a lesser extent in bipolar disorder. We propose that these findings indicate reduced intracortical myelin. In accordance with the corollary discharge hypothesis, this could cause disinhibition of sensory input, resulting in distorted perceptual processing leading to the characteristic positive symptoms of schizophrenia.

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