Neuroscience
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Interferon-alpha (IFN-α) is an important mediator of antiviral immune responses. It is also used clinically in the treatment of hepatitis-C infection. Though effective, IFN-α-based therapies can often impair mood, motivation and cognition, which when severe can appear indistinguishable from major depression. ⋯ Acute changes in striatal microstructure additionally predicted the continued development of fatigue but not mood symptoms 4 and 8 weeks later into treatment. Our findings highlight the value of NODDI as a potential in vivo biomarker of the central effects of peripheral inflammation. We highlight the exquisite sensitivity of the striatum to IFN-α and further implicate striatal perturbation in IFN-α-induced fatigue.
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The recent introduction of advanced magnetic resonance (MR) imaging techniques to characterize focal and global degeneration in multiple sclerosis (MS), like the Composite Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available new tools to image axonal pathology non-invasively in vivo. These methods already showed greater sensitivity and specificity compared to conventional diffusion tensor-based metrics (e.g., fractional anisotropy), overcoming some of its limitations. ⋯ For comparison, we contrasted the ability of fractional anisotropy measurements to uncover differences between lesion, normal-appearing white matter (WM), gray matter and healthy tissue under the same imaging protocols. We show that: (1) focal and diffuse differences in several microstructural parameters are observed under clinical settings; (2) advanced models (CHARMED, DKI and NODDI) have increased specificity and sensitivity to neurodegeneration when compared to fractional anisotropy measurements; and (3) both high (3 T) and ultra-high fields (7 T) are viable options for imaging tissue change in MS lesions and normal appearing WM, while higher b-values are less beneficial under the tested short-time (10 min acquisition) conditions.
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The process of neurovascular coupling ensures that increases in neuronal activity are fed by increases in cerebral blood flow. Evidence suggests that neurovascular coupling may be impaired in Multiple Sclerosis (MS) due to a combination of brain hypoperfusion, altered cerebrovascular reactivity and oxygen metabolism, and altered levels of vasoactive compounds. Here, we tested the hypothesis that neurovascular coupling is impaired in MS. ⋯ Gamma power reduction could be an indicator of GM dysfunction, possibly mediated by GABAergic changes. Altered hemodynamic responses confirm previous reports of a vascular dysfunction in MS. Despite altered neuronal and vascular responses, neurovascular coupling appears to be preserved in MS, at least within the range of damage and disability studied here.
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Neuroinflammatory pathology has long been identified to contribute to the pathology of Parkinson disease. Early microstructural changes in white matter tracts might give a clue for earlier detection of PD. We investigated through diffusion MRI connectometry the structural correlates of white matter tracts of 81 patients with PD with whole blood neutrophil-to-lymphocyte ratio (NLR), controlling for age and sex. ⋯ The spin distribution function (SDF) values were used in DMRI connectometry analysis. The connectometry analyses identified white matter QA of the following fibers to be correlated with NLR score after adjustment for age and sex: bilateral cingulum, body and left crus of fornix, bilateral corticospinal tract (CST), and body and splenium of corpus callosum (CC) and superior cerebellar peduncle with decreased connectivity related to NLR (FDR = 0.04542). Keeping with emerging evidence on the role of neuroinflammation in PD pathology, these results with functional relevance to prodromal Parkinson disease, bring new insights to pivotal role of peripheral inflammation in CNS neurodegeneration.
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Our recent studies demonstrated that electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) are promising MRI probes for detecting various pathological aspects of autoimmunity in the central nervous system (CNS). However, investigation of the precise tissue and cellular distribution of VSOP has been technically limited due to the need to use iron detection methods for VSOP visualization. Therefore, we assessed here the utility of europium (Eu)-doped VSOP as an MRI tool for in vivo investigations in the animal model experimental autoimmune encephalomyelitis (EAE), and as a tool to investigate histopathological processes in the CNS using fluorescence microscopy. ⋯ Within the choroid plexus, Eu-VSOP were associated both with monocytes/macrophages present in the plexus stroma, and associated with epithelial cells. Using Eu-VSOP, we demonstrated for the first time the involvement of the choroid plexus in relapses. Thus, Eu-VSOP have the potential to reveal various aspects of choroid plexus involvement in neuroinflammation, including monocyte recruitment from the blood and alterations of the choroid plexus epithelium.