Post-mortem assessment of rat spinal cord injury and white matter sparing using inversion recovery-supported proton density magnetic resonance imaging

Scholtes, Félix; Theunissen, Evi; Phan-Ba, Rémy; Adriaensens, Peter; Brook, Gary; Franzen, Rachelle; Gelan, Jan; Schoenen, Jean; Martin, Didier

doi:10.1038/sc.2010.129

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…From one side, SXPCT was used to assess cells or tissue damage following SCI, overcoming common problems due to the lower spatial resolution of other soft-tissue 3D imaging techniques. [36][37][38][39][40] On the other hand, histology combined with immunohistochemistry provides complementary information due to its specific identification of nervous cell types based on their biomarker expression profile. Major advantages of SXPCT image analysis include the direct 3D cell quantification within a volume-of-interest, avoiding many of the technical issues during sample preparation as in the case of stereology (unreliable serial sectioning, variation in staining intensities).…”

Section: Discussionmentioning

confidence: 99%

Lesion Extension and Neuronal Loss after Spinal Cord Injury Using X-Ray Phase-Contrast Tomography in Mice

Maugeri

Jankovski

Malucelli

et al. 2023

Journal of Neurotrauma

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Following a spinal cord injury (SCI) the degree of function (motor, autonomous, or sensory) correlates with the severity of nervous tissue disruption. An imaging technique able to capture non-invasively and simultaneously the complex mechanisms of neuronal loss, vascular damage, and peri-lesional tissue reorganization is currently lacking in experimental SCI studies. Synchrotron X-ray phase-contrast tomography (SXPCT) has emerged as a non-destructive threedimensional (3D) neuroimaging technique with high contrast and spatial resolution. In this framework, we developed a multi-modal approach combining SXPCT, histology and correlative methods to study neurovascular architecture in normal and spinal level C4-contused mouse spinal cords (C57BL/6J mice, age 2-3 months). The evolution of SCI lesion was imaged at the cell resolution level during the acute (30 min) and subacute (7 day) phases. Spared motor neurons (MNs) were segmented and quantified in different volumes localized at and away from the epicenter. SXPCT was able to capture neuronal loss and blood-brain barrier breakdown following SCI. Three-dimensional quantification based on SXPCT acquisitions showed no additional MN loss between 30 min and 7 days post-SCI. In addition, the analysis of hemorrhagic (at 30 min) and lesion (at 7 days) volumes revealed a high similarity in size, suggesting no extension of tissue degeneration between early and later time-points. Moreover, glial scar borders were unevenly distributed, with rostral edges being the most extended. In conclusion, SXPCT capability to image at high resolution cellular changes in 3D enables the understanding of the relationship between hemorrhagic events and nervous structure damage in SCI.

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Section: Discussionmentioning

confidence: 99%

Lesion Extension and Neuronal Loss after Spinal Cord Injury Using X-Ray Phase-Contrast Tomography in Mice

Maugeri

Jankovski

Malucelli

et al. 2023

Journal of Neurotrauma

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“…5,[52][53][54][55] It would be useful for prognosis and possibly as a biomarker of response to therapy if…”

Section: Diffusion Tensor Imagingmentioning

confidence: 99%

Spinal Cord Injury: How Can We Improve the Classification and Quantification of Its Severity and Prognosis?

Krishna

Andrews

Varma

et al. 2014

Journal of Neurotrauma

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The preservation of functional neural tissue after spinal cord injury (SCI) is the basis for spontaneous neurological recovery. Some injured patients in the acute phase have more potential for recovery than others. This fact is problematic for the construction of clinical trials because enrollment of subjects with variable recovery potential makes it difficult to detect effects, requires large sample sizes, and risks Type II errors. In addition, the current methods to assess injury and recovery are non-quantitative and not sensitive. It is likely that therapeutic combinations will be necessary to cause substantially improved function after SCI, thus we need highly sensitive techniques to evaluate changes in motor, sensory, autonomic and other functions. We review several emerging neurophysiological techniques with high sensitivity. Quantitative methods to evaluate residual tissue sparing after severe acute SCI have not entered widespread clinical use. This reduces the ability to correlate structural preservation with clinical outcome following SCI resulting in enrollment of subjects with varying patterns of tissue preservation and injury into clinical trials. We propose that the inclusion of additional measures of injury severity, pattern, and individual genetic characteristics may enable stratification in clinical trials to make the testing of therapeutic interventions more effective and efficient. New imaging techniques to assess tract injury and demyelination and methods to quantify tissue injury, inflammatory markers, and neuroglial biochemical changes may improve the evaluation of injury severity, and the correlation with neurological outcome, and measure the effects of treatment more robustly than is currently possible. The ability to test such a multimodality approach will require a high degree of collaboration between clinical and research centers and government research support. When the most informative of these assessments is determined, it may be possible to identify patients with substantial recovery potential, improve selection criteria and conduct more efficient clinical trials.

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“…Even in the case of concrete concepts such as tissue sparing, there is little consensus on how to best quantify changes. There have been a variety of approaches taken for histopathological quantification (38, 90, 259, 264, 276–284). In the older literature, histological analyses of SCI consisted of qualitative descriptions of “typical” cords from each experimental condition (259).…”

Section: Multiple Measurement Techniques For the Same Featurementioning

confidence: 99%

Syndromics: A Bioinformatics Approach for Neurotrauma Research

Ferguson

Stück

Nielson

2011

Transl. Stroke Res.

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Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings.

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Post-mortem assessment of rat spinal cord injury and white matter sparing using inversion recovery-supported proton density magnetic resonance imaging

Cited by 7 publications

References 15 publications

Lesion Extension and Neuronal Loss after Spinal Cord Injury Using X-Ray Phase-Contrast Tomography in Mice

Lesion Extension and Neuronal Loss after Spinal Cord Injury Using X-Ray Phase-Contrast Tomography in Mice

Spinal Cord Injury: How Can We Improve the Classification and Quantification of Its Severity and Prognosis?

Syndromics: A Bioinformatics Approach for Neurotrauma Research

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