Tracking the neurodegenerative gradient after spinal cord injury

Azzarito, Michela; Seif, Maryam; Kyathanahally, Sreenath Pruthviraj; Curt, Armin; Freund, Patrick

doi:10.1016/j.nicl.2020.102221

Cited by 23 publications

(37 citation statements)

References 35 publications

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“…The number of components (k) for subsequent ICA were estimated using a principled information theoretic approach (rather than arbitrarily selecting the number of components 26 ). ICA was then applied to the T1w WM images of 23 The mixing matrix was used for subsequent statistical analysis, where every column of the mixing matrix quantifies the contribution of each component to the 53 subjects. An ANOVA was applied to each column to assess which components showed a significant group difference, adjusted for covariates of no interest (ie, age, gender, total intracranial volume (TIV) and scanner).…”

Section: Discussionmentioning

confidence: 99%

“…We used SPM12 spatial routines on the T1w images and MPM maps. As a novelty, we used a brain plus spinal cord (BSC) template 23 covering the brain and the upper cervical spinal cord in the unified segmentation approach, 24 which allowed us to assess brain and cervical cord changes within the same statistical framework. This BSC template was specified as a tissue probability map (ie, spatial prior) in the unified segmentation step.…”

Section: Discussionmentioning

confidence: 99%

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Microstructural plasticity in nociceptive pathways after spinal cord injury

Kyathanahally

Azzarito

Rösner

et al. 2021

J Neurol Neurosurg Psychiatry

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ObjectiveTo track the interplay between (micro-) structural changes along the trajectories of nociceptive pathways and its relation to the presence and intensity of neuropathic pain (NP) after spinal cord injury (SCI).MethodsA quantitative neuroimaging approach employing a multiparametric mapping protocol was used, providing indirect measures of myelination (via contrasts such as magnetisation transfer (MT) saturation, longitudinal relaxation (R1)) and iron content (via effective transverse relaxation rate (R2*)) was used to track microstructural changes within nociceptive pathways. In order to characterise concurrent changes along the entire neuroaxis, a combined brain and spinal cord template embedded in the statistical parametric mapping framework was used. Multivariate source-based morphometry was performed to identify naturally grouped patterns of structural variation between individuals with and without NP after SCI.ResultsIn individuals with NP, lower R1 and MT values are evident in the primary motor cortex and dorsolateral prefrontal cortex, while increases in R2* are evident in the cervical cord, periaqueductal grey (PAG), thalamus and anterior cingulate cortex when compared with pain-free individuals. Lower R1 values in the PAG and greater R2* values in the cervical cord are associated with NP intensity.ConclusionsThe degree of microstructural changes across ascending and descending nociceptive pathways is critically implicated in the maintenance of NP. Tracking maladaptive plasticity unravels the intimate relationships between neurodegenerative and compensatory processes in NP states and may facilitate patient monitoring during therapeutic trials related to pain and neuroregeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Microstructural plasticity in nociceptive pathways after spinal cord injury

Kyathanahally

Azzarito

Rösner

et al. 2021

J Neurol Neurosurg Psychiatry

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“…It could be demonstrated in primates that quantitative MTsat is a robust parameter for tracking demyelination and loss of macromolecules after SCI [60]. Applied to SCI, MPMbased readouts could demonstrate reductions of myelinsensitive parameters and increase in iron content in areas undergoing atrophy [61][62][63][64]. This is suggestive of demyelination and iron deposition within these atrophying areas.…”

Section: Advanced Neuroimaging Markersmentioning

confidence: 99%

“…Changes in myelination and iron deposition were not only restricted to the proximity of the lesion site but also affected remote areas in both the spinal cord and the brain. Moreover, it could be demonstrated that these changes were correlated with longterm neurological outcome, speaking to their potential as new biomarkers for assessing injury severity and predicting outcome in SCI patients [61][62][63].…”

Section: Advanced Neuroimaging Markersmentioning

confidence: 99%

Improving Diagnostic Workup Following Traumatic Spinal Cord Injury: Advances in Biomarkers

Schading

Emmenegger

Freund

2021

Curr Neurol Neurosci Rep

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Purpose of Review Traumatic spinal cord injury (SCI) is a life-changing event with drastic implications for patients due to sensorimotor impairment and autonomous dysfunction. Current clinical evaluations focus on the assessment of injury level and severity using standardized neurological examinations. However, they fail to predict individual trajectories of recovery, which highlights the need for the development of advanced diagnostics. This narrative review identifies recent advances in the search of clinically relevant biomarkers in the field of SCI. Recent Findings Advanced neuroimaging and molecular biomarkers sensitive to the disease processes initiated by the SCI have been identified. These biomarkers range from advanced neuroimaging techniques, neurophysiological readouts, and molecular biomarkers identifying the concentrations of several proteins in blood and CSF samples. Some of these biomarkers improve current prediction models based on clinical readouts. Validation with larger patient cohorts is warranted. Summary Several biomarkers have been identified—ranging from imaging to molecular markers—that could serve as advanced diagnostic and hence supplement current clinical assessments.

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“…This gene also emerged as hub gene in a protein-protein interaction network based on Gene Expression Omnibus (GEO) database, including 1, 3, 7 and 14 DPL [35]. While several preclinical and clinical studies indicated substantial differences in the anatomical outcome of the SC segments rostral and caudal to the lesion [36,37], the supporting mechanisms are not clear. The secondary injury extension is not specular respect to the lesion epicentrum.…”

Section: Discussionmentioning

confidence: 99%

A Time-Course Study of the Expression Level of Synaptic Plasticity-Associated Genes in Un-Lesioned Spinal Cord and Brain Areas in a Rat Model of Spinal Cord Injury: A Bioinformatic Approach

Baldassarro

Sanna

Bighinati

et al. 2021

IJMS

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“Neuroplasticity” is often evoked to explain adaptation and compensation after acute lesions of the Central Nervous System (CNS). In this study, we investigated the modification of 80 genes involved in synaptic plasticity at different times (24 h, 8 and 45 days) from the traumatic spinal cord injury (SCI), adopting a bioinformatic analysis. mRNA expression levels were analyzed in the motor cortex, basal ganglia, cerebellum and in the spinal segments rostral and caudal to the lesion. The main results are: (i) a different gene expression regulation is observed in the Spinal Cord (SC) segments rostral and caudal to the lesion; (ii) long lasting changes in the SC includes the extracellular matrix (ECM) enzymes Timp1, transcription regulators (Egr, Nr4a1), second messenger associated proteins (Gna1, Ywhaq); (iii) long-lasting changes in the Motor Cortex includes transcription regulators (Cebpd), neurotransmitters/neuromodulators and receptors (Cnr1, Gria1, Nos1), growth factors and related receptors (Igf1, Ntf3, Ntrk2), second messenger associated proteins (Mapk1); long lasting changes in Basal Ganglia and Cerebellum include ECM protein (Reln), growth factors (Ngf, Bdnf), transcription regulators (Egr, Cebpd), neurotransmitter receptors (Grin2c). These data suggest the molecular mapping as a useful tool to investigate the brain and SC reorganization after SCI.

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Tracking the neurodegenerative gradient after spinal cord injury

Cited by 23 publications

References 35 publications

Microstructural plasticity in nociceptive pathways after spinal cord injury

Microstructural plasticity in nociceptive pathways after spinal cord injury

Improving Diagnostic Workup Following Traumatic Spinal Cord Injury: Advances in Biomarkers

A Time-Course Study of the Expression Level of Synaptic Plasticity-Associated Genes in Un-Lesioned Spinal Cord and Brain Areas in a Rat Model of Spinal Cord Injury: A Bioinformatic Approach

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