Micro‐diffusely abnormal white matter: An early multiple sclerosis lesion phase with intensified myelin blistering

Luchicchi, Antonio; Muñoz‐Gonzalez, Gema; Halperin, Saar T.; Strijbis, Eva; van Dijk, Laura H. M.; Foutiadou, Chrisa; Uriac, Florence; Bouman, Piet M.; Schouten, Maxime A. N.; Plemel, Jason; 't Hart, Bert A.; Geurts, Jeroen J. G.; Schenk, Geert J.

doi:10.1002/acn3.52015

Cited by 3 publications

References 57 publications

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Dynamic imaging of myelin pathology in physiologically preserved human brain tissue using third harmonic generation microscopy

Meijns,

Blokker,

Idema

et al. 2024

Preprint

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Myelin pathology is known to play a central role in disorders such as multiple sclerosis (MS) among others. Despite this, the pathological mechanisms underlying these conditions are often difficult to unravel. Conventional techniques like immunohistochemistry or dye-based approaches, do not provide a temporal characterization of the pathophysiological aberrations responsible for myelin changes in human specimens. Here, to circumvent this curb, we present a label-free, live-cell imaging approach of myelin using recent advancements in nonlinear harmonic generation microscopy applied to physiologically viable human brain tissue from post-mortem donors. Gray and white matter brain tissue from epilepsy surgery and post-mortem donors was excised. To sustain viability of the specimens for several hours, they were subjected to either acute or organotypic slice culture protocols in artificial cerebral spinal fluid. Imaging was performed using a femtosecond pulsed 1060 nm laser to generate second harmonic generation (SHG) and third harmonic generation (THG) signals directly from myelin and axon-like structures without the need to add any labels. Experiments on acute human brain slices and post-mortem human slice cultures reveal that myelin, along with lipid bodies, are the prime sources of THG signal. We show that tissue viability is maintained over extended periods during THG microscopy, and that prolonged THG imaging is able to detect experimentally induced subtle alterations in myelin morphology. Finally, we provide practical evidence that live-cell imaging of myelin with THG microscopy is a sensitive tool to investigate subtle changes in white matter of neurological donors. Overall, our findings support that nonlinear live-cell imaging is a suitable setup for researching myelin morphology in neurological conditions like MS.

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Dynamic imaging of myelin pathology in physiologically preserved human brain tissue using third harmonic generation microscopy

Meijns,

Blokker,

Idema

et al. 2024

Preprint

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Differential Analysis of Venous Sinus Diameters: Unveiling Vascular Alterations in Patients with Multiple Sclerosis

Tunç,

Danisan,

Taydas

et al. 2024

Diagnostics

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Background: Alterations in the cerebral venous system have been increasingly recognized as a significant component of the pathophysiology of multiple sclerosis (MS). This study aimed to explore the relationship between venous sinus diameter and MS to understand potential vascular alterations in MS patients compared with controls. We sought to determine whether these alterations were correlated with disease characteristics such as duration, lesion type, and disability score. Methods: This study included 79 MS patients diagnosed according to the 2017 McDonald criteria and 67 healthy individuals. Magnetic resonance imaging (MRI) scans via a 1.5 Tesla system provided measurements of the superior sagittal sinus, right and left transverse sinus, sinus rectus, and venous structures. Statistical analysis was conducted via SPSS, employing independent sample t tests, ANOVA, chi-square tests, and Pearson correlation analysis, with the significance level set at p < 0.05. Results: This study revealed significant differences in venous sinus diameter between MS patients and controls, with MS patients exhibiting larger diameters. Specifically, patients with brainstem and spinal lesions had larger diameters in certain sinus regions. No significant correlations were found between venous sinus diameter and demographic factors, expanded disability status scale scores, or lesion counts. However, a significant increase in perivenular lesions was noted in patients with longer disease durations. Conclusions: The findings indicate notable vascular alterations in MS patients, particularly in venous sinus diameters, suggesting a potential vascular component in MS pathology. The lack of correlation with conventional clinical and MRI metrics highlights the complexity of MS pathology. These insights underscore the need for further research, particularly longitudinal studies, to elucidate the role of venous changes in MS progression and their potential as therapeutic targets.

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Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond

Perdaens,

van Pesch

2024

IJMS

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Neurodegeneration is preeminent in many neurological diseases, and still a major burden we fail to manage in patient’s care. Its pathogenesis is complicated, intricate, and far from being completely understood. Taking multiple sclerosis as an example, we propose that neurodegeneration is neither a cause nor a consequence by itself. Mitochondrial dysfunction, leading to energy deficiency and ion imbalance, plays a key role in neurodegeneration, and is partly caused by the oxidative stress generated by microglia and astrocytes. Nodal and paranodal disruption, with or without myelin alteration, is further involved. Myelin loss exposes the axons directly to the inflammatory and oxidative environment. Moreover, oligodendrocytes provide a singular metabolic and trophic support to axons, but do not emerge unscathed from the pathological events, by primary myelin defects and cell apoptosis or secondary to neuroinflammation or axonal damage. Hereby, trophic failure might be an overlooked contributor to neurodegeneration. Thus, a complex interplay between neuroinflammation, demyelination, and neurodegeneration, wherein each is primarily and secondarily involved, might offer a more comprehensive understanding of the pathogenesis and help establishing novel therapeutic strategies for many neurological diseases and beyond.

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Micro‐diffusely abnormal white matter: An early multiple sclerosis lesion phase with intensified myelin blistering

Cited by 3 publications

References 57 publications

Dynamic imaging of myelin pathology in physiologically preserved human brain tissue using third harmonic generation microscopy

Dynamic imaging of myelin pathology in physiologically preserved human brain tissue using third harmonic generation microscopy

Differential Analysis of Venous Sinus Diameters: Unveiling Vascular Alterations in Patients with Multiple Sclerosis

Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond

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